Virtual reality simulation training in stroke thrombectomy centers with limited patient volume-Simulator performance and patient outcome.

BACKGROUND: Virtual reality simulation training may improve the technical skills of interventional radiologists when establishing endovascular thrombectomy at limited-volume stroke centers. The aim of this study was to investigate whether the technical thrombectomy performance of interventional radiologists improved after a defined virtual reality simulator training period. As part of the quality surveillance of clinical practice, we also assessed patient outcomes and thrombectomy quality indicators at the participating centers. METHODS: Interventional radiologists and radiology residents from three thrombectomy-capable stroke centers participated in a five months thrombectomy skill-training curriculum on a virtual reality simulator. The simulator automatically registered procedure time, the number of predefined steps that were correctly executed, handling errors, contrast volume, fluoroscopy time, and radiation dose exposure. The design was a before-after study. Two simulated thrombectomy cases were used as pretest and posttest cases, while seven other cases were used for training. Utilizing the Norwegian Stroke Register, we investigated clinical results in thrombectomy during the study period. RESULTS: Nineteen interventional radiologists and radiology residents participated in the study. The improvement between pretest and posttest cases was statistically significant for all outcome measures in both simulated cases, except for the contrast volume used in one case. Clinical patient outcomes in all three centers were well within the recommendations from multi-society consensus guidelines. CONCLUSION: Performance on the virtual reality simulator improved after training. Virtual reality simulation may improve the learning curve for interventional radiologists in limited-volume thrombectomy centers. No correlation alleged, the clinical data indicates that the centers studied performed thrombectomy in accordance with guideline-recommended standards.

Machine Learning Algorithms Versus Thresholding to Segment Ischemic Regions in Patients With Acute Ischemic Stroke.

OBJECTIVE: Computed tomography (CT) scan is a fast and widely used modality for early assessment in patients with symptoms of a cerebral ischemic stroke. CT perfusion (CTP) is often added to the protocol and is used by radiologists for assessing the severity of the stroke. Standard parametric maps are calculated from the CTP datasets. Based on parametric value combinations, ischemic regions are separated into presumed infarct core (irreversibly damaged tissue) and penumbra (tissue-at-risk). Different thresholding approaches have been suggested to segment the parametric maps into these areas. The purpose of this study is to compare fully-automated methods based on machine learning and thresholding approaches to segment the hypoperfused regions in patients with ischemic stroke. METHODS: We test two different architectures with three mainstream machine learning algorithms. We use parametric maps as input features, and manual annotations made by two expert neuroradiologists as ground truth. RESULTS: The best results are produced with random forest (RF) and Single-Step approach; we achieve an average Dice coefficient of 0.68 and 0.26, respectively for penumbra and core, for the three groups analysed. We also achieve an average in volume difference of 25.1 ml for penumbra and 7.8 ml for core. CONCLUSIONS: Our best RF-based method outperforms the classical thresholding approaches, to segment both the ischemic regions in a group of patients regardless of the severity of vessel occlusion. SIGNIFICANCE: A correct visualization of the ischemic regions will guide treatment decisions better.

Safety and Outcomes of Tenecteplase in Moderate and Severe Ischemic Stroke.

Background and Purpose- Tenecteplase represents a promising alternative to alteplase as thrombolytic treatment in acute ischemic stroke. There are limited data on tenecteplase 0.4 mg/kg in patients with increased stroke severity. We aimed to assess safety and efficacy of tenecteplase 0.4 mg/kg in patients with moderate and severe ischemic stroke. Methods- NOR-TEST (Norwegian Tenecteplase Stroke Trial) was a phase III trial designed to investigate the safety and efficacy of tenecteplase 0.4 mg/kg versus alteplase 0.9 mg/kg in ischemic stroke. In this post hoc analysis, moderate stroke was defined as admission National Institutes of Health Stroke Scale; 6 to 14 and severe stroke as National Institutes of Health Stroke Scale; ≥15. Rates of favorable outcome at 90 days, symptomatic intracerebral hemorrhage (sICH), and mortality after 7 and 90 days were assessed. Results- In patients with moderate stroke (n=261), there were no differences in rates of favorable outcome, sICH, or mortality between tenecteplase and alteplase. In patients with severe stroke (n=87), there were no differences in outcome, frequency of sICH, or mortality at 7 days, but all-cause mortality at 90 days was increased in patients treated with tenecteplase (10 [26.3%] versus 4 [9.1%]; P=0.045). One patient died of sICH in the tenecteplase group, and 2 patients died of sICH in the alteplase group. Conclusions- Rates of favorable outcome and sICH were similar between treatment groups in patients with moderate and severe stroke. Mortality after 90 days was increased in patients with severe stroke receiving tenecteplase. Future studies assessing tenecteplase 0.4 mg/kg should monitor safety parameters closely in patients with severe stroke. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01949948.

The epidemiology of dementia associated with Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative illness after Alzheimer's disease (AD). Cognitive impairment and dementia are common features in PD and characterized by a wide range of cognitive deficits distinct from those seen in AD. Mild cognitive impairment occurs even early in PD and is associated with shorter time to dementia. The purpose of this review is to present recent findings on clinical aspects of dementia in PD and to elucidate underlying clinical and neurobiological risk factors.

CSF amyloid-beta and tau proteins, and cognitive performance, in early and untreated Parkinson's disease: the Norwegian ParkWest study.

BACKGROUND: Alzheimer's disease (AD) pathology is found in a considerable portion of patients with Parkinson's disease (PD), particularly those with early dementia (PDD). Altered cerebrospinal fluid (CSF) levels of amyloid-ß (Aß) and tau proteins have been found in PDD, with intermediate changes for Aß42 in non-demented PD. The authors investigated whether AD-related CSF protein levels are altered and relate to neuropsychological performance in early, untreated PD. METHODS: CSF concentrations of Aß42, Aß40 and Aß38 were measured by electrochemiluminiscene and levels of total tau (T-tau) and phosphorylated tau (P-tau) by ELISA in 109 newly diagnosed, unmedicated, non-demented, community-based PD patients who had undergone comprehensive neuropsychological testing, and were compared with those of 36 age-matched normal controls and 20 subjects with mild AD. RESULTS: PD patients displayed significant reductions in Aß42 (19%; p=0.009), Aß40 (15.5%; p=0.008) and Aß38 (23%; p=0.004) but not T-tau (p=0.816) or P-tau (p=0.531) compared with controls. CSF Aß42 reductions in PD were less marked than in AD (53%; p=0.002). Sequential regression analyses demonstrated significant associations between CSF levels of Aß42 (ß=0.205; p=0.019), Aß40 (ß=0.378; p<0.001) and Aß38 (ß=0.288; p=0.001) and memory impairment, but not executive-attentional or visuospatial dysfunction. Tau protein levels did not correlate with cognitive measures. CONCLUSION: CSF Aß levels are altered in a subset of patients with early PD and relate to memory impairment. Our study suggests that alterations in Aß protein metabolism may contribute to the heterogeneity in pattern and course of cognitive decline associated with PD. Longitudinal studies are needed to clarify the clinical significance of CSF Aß peptides as prognostic biomarkers in PD.

The epidemiology of dementia associated with Parkinson disease.

Several recent studies have shown that dementia is common in Parkinson's disease (PD), and that in some patients, cognitive impairment occurs even at the time of diagnosis. The point prevalence of dementia in PD is close to 30% and the incidence rate is increased 4-6 times as compared to controls. The cumulative prevalence is very high, at least 75% of PD patients who survive for more than 10 years will develop dementia. The mean time from onset of PD to dementia is approximately 10 years. However, there are considerable variations, and some patients develop dementia early in the disease course. Earlier onset of dementia is associated with more structural brain changes. The most established risk factors for early dementia are old age, severity of motor symptoms, in particular postural and gait disturbances, mild cognitive impairment and visual hallucinations. The genetic contributions to dementia are currently not clear and need to be explored in future studies.

APOE alleles in Parkinson disease and their relationship to cognitive decline: a population-based, longitudinal study.

Apolipoprotein E gene alleles have been linked to various cardiovascular and neurodegenerative disorders. There have been conflicting reports of associations between Apolipoprotein E alleles and Parkinson disease and Parkinson disease dementia. To investigate the role of Apolipoprotein E alleles in Parkinson disease and Parkinson disease dementia, we have determined Apolipoprotein E genotypes in a group of patients with Parkinson disease (n = 95) and compared them with those of healthy control participants (n = 73). Additionally, in 64 longitudinally followed patients with Parkinson disease, the allele types were correlated to development and progression of dementia and to time from onset of Parkinson disease to dementia using multivariate and survival analyses. The Apolipoprotein E e4e4 genotype was more common in patients with Parkinson disease (7.4%) than in healthy controls (1.4%; P = .03). No significant associations between the Apolipoprotein E genotype and development and progression of dementia or time to dementia were found. More studies with larger Parkinson disease samples are warranted.

Late-onset familial amyloid polyneuropathy (FAP) Val30Met without family history.

Familial amyloid polyneuropathy (FAP) is rare and most commonly caused by the Val30Met mutation of the transthyretin (TTR) gene. Beside polyneuropathy, other complications due to amyloid deposits occur, but may vary in phenotype. The mutation tends to occur in endemic clusters. We describe a 65-year-old man from a non-endemic FAPVal30Met area who developed a progressive generalized painless axonal sensorimotor polyneuropathy with mild autonomic involvement and absent FAP symptoms in the family. Nerve biopsy showed amyloid deposits, staining with TTR-antibodies on immunohistochemistry. After DNA-sequencing of the TTR gene, the diagnosis of FAP Val30Met was made. Late-onset FAP Val30Met is a progressive and fatal disorder with varying penetrance, and may occur in non-endemic areas and cases without a family history.

FMR1 alleles in Parkinson's disease: relation to cognitive decline and hallucinations, a longitudinal study.

Carriers of expanded alleles of the fragile X mental retardation (FMR1) gene may display parkinsonism, cognitive decline, and behavioral changes. The authors screened 2 male groups of patients affected with Parkinson's disease (PD) (n = 137). One group (n = 56) was followed longitudinally for up to 12 years. Length of CGG repeats in PD patients was compared with healthy controls (n = 310). In addition, the association of the number of CGG repeats with cognitive decline or hallucinations was studied in the longitudinally followed PD group. The authors found no repeats in the premutation range (55-200 CGG repeats) and no significant difference in the proportion of intermediate-size (41-54 CGG repeats) carriers between the PD and the control groups. Using linear regression, the number of CGG repeats was not related to motor or cognitive progression. However, the marked cognitive decline in 2 patients carrying intermediate-size alleles points to a possible association. More studies with larger PD samples are warranted.

Associations between family history of Parkinson's disease and dementia and risk of dementia in Parkinson's disease: A community-based, longitudinal study.

Dementia is common in patients with Parkinson's disease (PDD). The etiology of PDD is still unclear, but exciting advances have been made in discovering pathogenetic components in Parkinson's disease (PD), implicating the role of genetic factors. It is, however, still controversial whether genetic factors also contribute to the development of dementia in PD. Thus, we investigated the association between development of dementia and a positive family history of PD or dementia in a community-based study of PD in Rogaland County, Norway (n = 219). The patients were followed prospectively with neurological and neuropsychological assessments. Dementia was more common in patients with a strong family association of PD (first-degree relatives > second-degree relatives > no family history; P < 0.05). However, time to dementia did not differ between the two groups. No associations between dementia in PD and familial occurrence of dementia could be shown. Further studies with larger samples are needed to explore a possible relationship between a family history of PD and development of dementia in PD and its potential pathogenetic mechanisms.

Familial occurrence of dementia and parkinsonism: a systematic review.

Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are common clinical dementias characterized neuropathologically by the presence of cortical Lewy body pathology and with distinct clinical and neurobiological similarities. Importantly, genetic factors seem to play a key role in the pathogenesis of Parkinson's disease. In the current article, we examine the evidence for a genetic component to DLB and PDD by reviewing studies of familial PDD and DLB as well as familial coincidental PDD and DLB, and report the genes involved. There is a convincing genetic overlap between both syndromes, suggesting that they share a common etiological factor.