A recommendation for applied researchers to substantiate the claim that ordinal variables are the product of underlying bivariate normal distributions.

A simulation study was carried out to study the behaviour of the polychoric correlation coefficient in data not compliant with the assumption of underlying continuous variables. Such data can produce relatively high estimated polychoric correlations (in the order of .62). Applied researchers are prone to accept these artefacts as input for elaborate modelling (e.g., structural equation models) and inferences about reality justified by sheer magnitude of the correlations. In order to prevent this questionable research practice, it is recommended that in applications of the polychoric correlation coefficient, data is tested with goodness-of-fit of the BND, that such statistic is reported in published applications, and that the polychoric correlation is not applied when the test is significant.

Organ data from the developing Göttingen minipig: first steps towards a juvenile PBPK model.

The Göttingen minipig is the most commonly used pig breed in preclinical drug development in Europe and has recently also been explored for physiologically based pharmacokinetic modelling. To develop such a model, not only physiological data from adult animals but also data from juvenile animals are required, especially when using this model for paediatric drug development. Therefore, the aim of our study was to document body and organ weights (brain, heart, lungs, liver, gastrointestinal tract, spleen and kidney), lengths of the small and large intestines and pH values of the gastrointestinal tract in Göttingen minipigs from the foetal stage until the age of 5 months. Postnatal organ and body weights were fitted to regression models to find suitable equations that could be used to estimate organ weights as a function of body weight in the neonatal and juvenile Göttingen minipig. Most organs followed a non-linear growth curve during the first 5 months of life. In general, relative organ weights were the highest during the first week of life, during which the gastric pH was more alkaline than at 28 days of age.

Subcortical vascular cognitive impairment, no dementia: EEG global power independently predicts vascular impairment and brain symmetry index reflects severity of cognitive decline.

BACKGROUND AND PURPOSE: Vascular cognitive impairment, no dementia (vCIND) is a prevalent and potentially preventable disorder. Clinical presentation of the small-vessel subcortical subtype may be insidious, and differential difficulties can arise with mild cognitive impairment. We investigated EEG parameters in subcortical vCIND in comparison with amnestic multidomain mild cognitive impairment to determine the additional diagnostic value of quantitative EEG in this setting. METHODS: Fifty-seven community-residing patients with an uneventful central neurologic history and first presentation of cognitive decline without dementia were included. Neuropsychological test results were correlated with EEG parameters. Predictive values for vCIND and amnestic multidomain mild cognitive impairment were calculated using receiver operating characteristic curves and logistic regression modeling. RESULTS: Vascular cognitive impairment, no dementia and amnestic multidomain mild cognitive impairment differed with regard to the EEG (delta + theta)/(alpha + beta) ratio (DTABR) and pairwise derived brain symmetry index. We found statistically significant correlations between pairwise derived brain symmetry index and immediate verbal memory, immediate global memory, verbal recognition, working memory, and mean memory score in vCIND. Verbal fluency (odds ratio: 1.54, 95% confidence interval: 1.04-2.28, P = 0.033) and (delta + theta)/(alpha + beta) ratio (odds ratio: 2.28, 95% confidence interval: 1.06-4.94, P = 0.036) emerged as independent diagnostic predictors for vCIND with an overall correct classification rate of 95.0%. CONCLUSION: Our data indicate that EEG is of additional value in the differential diagnosis and follow-up of patients presenting with cognitive decline. These findings may have an impact on memory care.

EEG in silent small vessel disease: sLORETA mapping reveals cortical sources of vascular cognitive impairment no dementia in the default mode network.

INTRODUCTION: Vascular cognitive impairment, no dementia (vCIND) is a prevalent and potentially preventable disorder. Clinical presof the small vessel subcortical subtype may be insidious and difficult to diagnose in the initial stage. We investigated electroencephalographic sources of subcortical vCIND in comparison to amnesic multidomain mild cognitive impairment (amdMCI) to determine the additional diagnostic value of quantitative electroencephalograhy (EEG) in this setting. METHODS: Fifty-seven community residing patients with an uneventful central neurological history and first presentation of cognitive decline without dementia were included, 35 patients were diagnosed with vCIND and 22 with amdMCI. A cognitive control group, deliberately recruited from a cerebrovascular impaired cohort, consisted of cognitively healthy participants who experienced a fully recovered first ever transient ischemic attack (TIA) without clinical or magnetic resonance imaging evidence of stroke. From standard EEGs, the differences in standardized low-resolution brain electromagnetic tomography (sLORETA) sources were determined for the discrete frequency ranges 1-4 (delta), 4-8 (theta), 8-10.5 (alpha1), 10.5-13 (alpha2), 13-22 (beta1), and 22-30 (beta2) Hz. RESULTS: In vCIND, a statistically significant decrease in parietooccipital alpha1 relative power current density compared with TIA and mild cognitive impairment patients was found. There was a significant decrease in frontal and parietooccipital beta1 relative power current density in vCIND compared with TIA patients. A significant increase in (pre) frontal delta relative power current density in vCIND compared with amdMCI was found as well. In amdMCI, delta relative power current density was significantly increased in the core limbic system. DISCUSSION: Cortical sources of abnormal EEG activity in regions implicated in the default mode network are revealed by sLORETA at an early stage in vascular cognitive impairment. Mapping of parietooccipital alpha1, frontoparietooccipital beta1 and (pre) frontal delta loci in vCIND may reflect early executive and visuospatial dysfunction in this cohort. Standard EEG with sLORETA mapping might be an additional, noninvasive, and cost-effective tool in the diagnostic workup of patients presenting with a cognitive decline.

Quantitative EEG in ischemic stroke: correlation with functional status after 6 months.

OBJECTIVE: Stroke is a major cause of adult-onset disability and dependency. We investigated whether EEG parameters are of prognostic value for functional outcome 6 months after ischemic stroke. METHODS: One-hundred and ten patients presenting with acute ischemic stroke and persistent neurological deficits at EEG recording were incrementally included. Clinical characteristics, volume of ischemia and EEG parameters were correlated with functional outcome assessed with the modified Rankin Scale (mRS) score. Predictive values for disability, dependency and death were calculated using receiver operating characteristic (ROC) curves and logistic regression modeling. RESULTS: The EEG pairwise derived Brain Symmetry Index (pdBSI) and (delta+theta)/(alpha+beta) ratio (DTABR) were significantly correlated with the modified Rankin Scale (mRS) score at month 6 (Spearman ρ=0.46 and ρ=0.47, respectively, p<0.0005 for both). NIHSS (OR 1.15, 95% CI 1.04-1.27, p=0.005) and pdBSI (OR 4.07, 95% CI 1.32-12.58, p=0.015) were independently associated with disability 6 months after stroke. Dependency was independently indicated by NIHSS (OR 1.22, 95% CI 1.09-1.37, p<0.0005) and DTABR (OR 2.25, 95% CI 1.16-4.37, p=0.016). Six month mortality was independently indicated by age at stroke onset (OR 1.18, 95% CI 1.05-1.32, p=0.007), NIHSS (OR 1.11, 95% CI 1.03-1.21, p=0.009) and DTABR (OR 2.04, 95% CI 1.08-3.85, p=0.028). CONCLUSIONS: EEG in the subacute setting of ischemic stroke may be of prognostic value for disability, dependency and death after 6 months. SIGNIFICANCE: Early prognostication of functional outcome after stroke is relevant to efficient rehabilitation management to enhance recovery and minimize long-term disability.

Quantitative EEG in ischemic stroke: correlation with infarct volume and functional status in posterior circulation and lacunar syndromes.

OBJECTIVE: The significant impact of stroke on health care results in an unmet need for efficient stroke care in resources limited environments. Practical, inexpensive and easy to obtain predictive EEG parameters have been suggested in anterior circulation syndromes. We investigated whether EEG parameters are of additional predictive value with regard to lesion volume and short-term functional outcome in lacunar (LACS) and posterior circulation (POCS) syndromes of presumed ischemic origin. METHODS: Sixty (60) patients presenting with LACS or POCS were incrementally included. EEG parameters were correlated with volume of ischemia and functional status. Predictive values for definite stroke and unfavourable outcome were calculated using receiver operating characteristic (ROC) curves and logistic regression modelling. RESULTS: The pairwise derived brain symmetry index (pdBSI) emerged as independent predictor for definite stroke in patients presenting with LACS and POCS (odds ratio (OR) 2.69, 95% confidence interval (CI) 1.24-5.82, p=0.012) and in patients with a National Institutes of Health Stroke Scale (NIHSS) score of 0 at EEG recording (OR 7.67, 95% CI 1.24-47.32, p=0.026). In ROC analysis, the (delta+theta)/(alpha+beta) ratio (DTABR) predicted unfavourable outcome at day 7 with an accuracy of 83% in LACS but not in POCS. In logistic regression, unfavourable outcome in LACS was predicted by nominal NIHSS with marginal significance (OR 1.84, 95% CI 1.00-3.37, p=0.05), while in categorical modelling, DTABR>2.4 displayed a statistically significant ominous odd ratio of 13.00 (95% CI 1.11-152.35, p=0.041) with identical predicted and observed values. CONCLUSIONS: EEG may be of additional value by confirming or excluding definite stroke after resolution of symptoms in lacunar and posterior circulation syndromes of presumed ischemic origin and prognosticating short-term functional status in lacunar syndrome. SIGNIFICANCE: These findings may have an impact on stroke care.

Additional value of quantitative EEG in acute anterior circulation syndrome of presumed ischemic origin.

OBJECTIVE: The clinical course of acute stroke can be highly variable and for effective management outcome prediction needs to be refined. We investigated whether EEG parameters are of additional diagnostic and prognostic value in the early phase of acute ischemic anterior circulation stroke. METHODS: Ninety-four patients presenting with acute anterior circulation syndrome (ACS) of presumed ischemic origin were incrementally included. Clinical characteristics were correlated with volume of ischemia and EEG parameters. Predictive values for definite stroke, early neurological deterioration, spontaneous early neurological improvement and death within 1 week after ACS were calculated using ROC curves and logistic regression modelling. RESULTS: In patients with normal or near normal NIHSS score of 0 or 1, the pairwise derived brain symmetry index (pdBSI) was an independent predictor for definite stroke displaying an overall accuracy of 80%. Early neurological deterioration was independently predicted by pdBSI with a correct classification rate of 95%. In ROC analysis, death was predicted by pdBSI with overall accuracy of 97%. Spontaneous neurological improvement was independently predicted by the delta+theta/alpha+beta - ratio with overall accuracy of 75%. Small-vessel stroke was independently predicted by pdBSI with a correct classification rate of 92%. CONCLUSIONS: EEG may be of prognostic value for spontaneous neurological improvement, early neurological deterioration and death in the acute setting of acute anterior circulation syndrome of presumed ischemic origin. SIGNIFICANCE: These findings may have an impact on stroke care.

Reproducibility and clinical relevance of quantitative EEG parameters in cerebral ischemia: a basic approach.

OBJECTIVE: To investigate reproducibility and clinical relevance of quantitative EEG parameters in ischemic cerebrovascular disease. METHODS: EEG was recorded in 31 patients suffering from subacute ischemic cerebrovascular disease. Ten age-matched control subjects were included as a reference group. Intra-recording, intrarater and interrater reproducibility was calculated for standard EEG measures and for a pair wise derived Brain Symmetry Index (pdBSI). Correlations between EEG parameters, clinical status and volume of ischemia on diffusion weighted imaging (DWI) were calculated. RESULTS: pdBSI was sensitive to asymmetry in the amplitude and frequency domain in a random white noise model and in a simulated sinusoidal model. Minimal Cronbach alpha for intra-recording, intra- and inter-rater reproducibility ranged between 0.95 and 0.99 for standard spectral parameters and between 0.96 and 0.99 for pdBSI. We found a significant difference in pdBSI between stroke patients and control or TIA (p=0.0003). pdBSI correlated significantly with NIH stroke scale at admission and DWI volume across different levels of stroke probability (Spearman's rho=0.64-0.70 and 0.79-0.84, respectively, p<0.00001 for both). CONCLUSIONS: pdBSI displays high multilevel reproducibility and reliably discriminates between stroke and TIA patients or control subjects, and correlates significantly with clinical and radiological status. SIGNIFICANCE: Based on this methodological analysis, reliable EEG parameters can be evaluated in a general stroke population for clinically relevant state and outcome measures.