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OBJECTIVE: The Swiss guidelines for driving with epilepsy require that electroencephalogram (EEG) findings must be compatible with the fitness to drive (FTD) without specifying any criteria. This nationwide survey investigated how Swiss neurologists implement this requirement in clinical practice. METHODS: An online survey, including 19 EEG examples and statements about the compatibility of the EEG with FTD, was distributed to all members of the Swiss Society of Clinical Neurophysiology and all Swiss neurological clinics with residency programs. Descriptive statistics and Fleiss' Kappa for inter-rater agreement were performed. RESULTS: 102 participants (37% female, 45% <45 years) completed the survey, with 15% primarily working in a specialized epileptology center (EPI), 55% in a hospital setting without epileptological focus (HOS), and 30% in private practice (PP). Most participants of all three groups regarded EEG normal variants as compatible with FTD, while hyperventilation-induced rhythmic slowing and some pathological patterns (e.g., frontal and temporal intermittent rhythmic delta activity [FIRDA, TIRDA], focal interictal epileptiform discharges [IED], focal seizure) were evaluated more heterogeneously. The EEG inter-rater agreement for EPI was 0.4; 0.31 for PP; and 0.24 for HOS. No consensus was found for acceptable duration for generalized or focal IEDs. Among all participants, evaluation by an epilepsy center (85%) and reaction-time testing (67%) were evaluated as the most useful additional examinations. However, reaction-time testing is rarely or never performed by 58%. Most supported EEG results as part of the FTD assessment and demanded more research (both 82%). SIGNIFICANCE: Our survey indicates considerable heterogeneity among Swiss neurologists when evaluating the EEG findings for FTD. Inter-rater agreement in all three groups was fair, with highest agreement among epileptologists. We noted a discrepancy between the usefulness and actual application of reaction-time testing. More training and research are warranted to achieve rater-independent consistency for FTD evaluation. PLAIN LANGUAGE SUMMARY: In Switzerland, neurologists must consider the findings from EEG (brain waves) exams to evaluate driving safety in people with epilepsy. We surveyed Swiss neurologists, asking their opinions on this matter. We found that opinions differ among individual doctors, with the highest agreement among epilepsy specialists. We also found that some additional tests, such as reaction-time testing, are perceived as useful but are rarely performed. The participating neurologists supported considering EEG results for driving fitness assessments but favored more precise guidelines and research.
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OBJECTIVE: To explore associations of the main component (P100) of visual evoked potentials (VEP) to pre- and postchiasmatic damage in multiple sclerosis (MS). METHODS: 31 patients (median EDSS: 2.5), 13 with previous optic neuritis (ON), and 31 healthy controls had VEP, optical coherence tomography and magnetic resonance imaging. We tested associations of P100-latency to the peripapillary retinal nerve fiber layer (pRNFL), ganglion cell/inner plexiform layers (GCIPL), lateral geniculate nucleus volume (LGN), white matter lesions of the optic radiations (OR-WML), fractional anisotropy of non-lesional optic radiations (NAOR-FA), and to the mean thickness of primary visual cortex (V1). Effect sizes are given as marginal R2 (mR2). RESULTS: P100-latency, pRNFL, GCIPL and LGN in patients differed from controls. Within patients, P100-latency was significantly associated with GCIPL (mR2 = 0.26), and less strongly with OR-WML (mR2 = 0.17), NAOR-FA (mR2 = 0.13) and pRNFL (mR2 = 0.08). In multivariate analysis, GCIPL and NAOR-FA remained significantly associated with P100-latency (mR2 = 0.41). In ON-patients, P100-latency was significantly associated with LGN volume (mR2 = -0.56). CONCLUSIONS: P100-latency is affected by anterior and posterior visual pathway damage. In ON-patients, damage at the synapse-level (LGN) may additionally contribute to latency delay. SIGNIFICANCE: Our findings corroborate post-chiasmatic contributions to the VEP-signal, which may relate to distinct pathophysiological mechanisms in MS.
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Potenciais Evocados Visuais , Corpos Geniculados , Esclerose Múltipla , Vias Visuais , Humanos , Masculino , Feminino , Corpos Geniculados/fisiopatologia , Corpos Geniculados/diagnóstico por imagem , Adulto , Potenciais Evocados Visuais/fisiologia , Vias Visuais/fisiopatologia , Vias Visuais/diagnóstico por imagem , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Imageamento por Ressonância Magnética , Neurite Óptica/fisiopatologia , Neurite Óptica/diagnóstico por imagemRESUMO
Neurotoxicity is a well-described adverse effect of cefepime. Clinical presentation includes mild neurological deficits, aphasia, impairment of consciousness, and even nonconvulsive status epilepticus. Impaired kidney function is considered the most important risk factor for cefepime-induced neurotoxicity (CIN) and frequently occurs during the course of critical diseases with concomitant acute kidney injury (AKI). Physicians should be aware of situations with increased risk of AKI and the preventive actions required to reduce the risk of CIN. We present three patients with AKI who were treated with cefepime for healthcare-associated infections. Subsequently, two patients developed CIN demonstrating very high cefepime levels in plasma. In the third patient, CIN was likely prevented as the increased risk of neurotoxicity was noted and cefepime treatment was ceased immediately. Diagnosis of CIN might be challenging due to various causes of encephalopathy, in particular in the setting of severely ill patients. Electroencephalogram may assist in establishing the diagnosis, in particular when cefepime therapeutic drug monitoring is not available. As CIN is potentially reversible, it is an important differential diagnosis to consider especially in patients with impaired renal function or being susceptible to AKI. Preventive measures of CIN include therapeutic drug monitoring, consideration of a therapeutic alternative, awareness regarding a potential overestimation of the glomerular filtration rate, and electronic health record alerts about risk constellations for potential overdosing.
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Background: Diagnosis of Amyotrophic Lateral Sclerosis (ALS) is challenging as initial presentations are various and diagnostic biomarkers are lacking. The diagnosis relies on the presence of both upper and lower motor neuron signs and thorough exclusion of differential diagnoses, particularly as receiving an ALS diagnosis has major implications for the patient. Sjögren's syndrome may mimic peripheral ALS phenotypes and should be considered in the work-up. Case: A 72-year-old female presented with a mono-neuropathy of the right leg and a complaint of dry eyes and mouth. Initial diagnostic work-up confirmed a regional sensorimotor neuropathy and a Sjögren's syndrome; a causal relationship was assumed. However, motor symptoms spread progressively despite immunosuppressive treatment, eventually including both legs, both arms and the diaphragm. Clinically, unequivocal central signs were lacking, but further along in the disease course, the atrophy pattern followed a split phenotype and deep tendon reflexes were preserved. Nerve biopsy did not show vasculitic infiltration; however, serum neurofilament light chain (sNfL) concentrations were and remained persistently highly elevated despite immunosuppressive treatment. Electrodiagnostic re-evaluation confirmed denervation in 3 regions. A diagnosis of familial ALS was finally confirmed by a C9orf 72 repeat expansion. Stationary sensory symptoms were best explained by a neuropathy associated with concomitant Sjögren's syndrome. Discussion: Our instructive case shows the difficulties of diagnosing ALS in the setting of a peripheral symptom onset and a concurrent but unrelated condition also causing neuropathy. Such cases require high clinical vigilance and readiness to reappraise diagnostic findings if the disease course deviates from expectation. Recently proposed simplified diagnostic criteria, genetic testing and body fluid biomarkers such as sNfL may facilitate the diagnostic process and lead to an earlier diagnosis of ALS.
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SUMMARY: Evoked potentials (EPs) measure quantitatively and objectively the alterations of central signal propagation in multiple sclerosis and have long been used for diagnosis. More recently, their utility for prognosis has been demonstrated in several studies, summarizing multiple EP modalities in a single score. In particular, visual, somatosensory, and motor EPs are useful because of their sensitivity to pathology in the frequently affected optic nerve, somatosensory tract, and pyramidal system. Quantitative EP scores show higher sensitivity to change than clinical assessment and may be used to monitor disease progression. Visual EP and the visual system have served as a model to study remyelinating therapies in the setting of acute and chronic optic neuritis. This review presents rationale and evidence for using multimodal EP as prognostic and response biomarkers in clinical trials, targeting remyelination or halting disease progression in multiple sclerosis.
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Ensaios Clínicos como Assunto , Potenciais Evocados/fisiologia , Esclerose Múltipla , Adulto , Progressão da Doença , Humanos , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla/terapia , Prognóstico , Resultado do TratamentoRESUMO
Objective: To evaluate the sensitivity to change of differently calculated quantitative scores from motor evoked potentials (MEP) in patients with primary progressive multiple sclerosis (PPMS). Methods: Twenty patients with PPMS had MEP to upper and lower limbs at baseline, years 1 and 2 measured in addition to clinical assessment [Expanded Disability Status Scale (EDSS), ambulation score]; a subsample (n = 9) had a nine-hole peg test (NHPT) and a timed 25-foot walk (T25FW). Quantitative MEP scores for upper limbs (qMEP-UL), lower limbs (qMEP-LL), and all limbs (qMEP) were calculated in three different ways, based on z-transformed central motor conduction time (CMCT), shortest corticomuscular latency (CxM-sh), and mean CxM (CxM-mn). Changes in clinical measures and qMEP metrics were analyzed by repeated-measures analysis of variance (rANOVA), and a factor analysis was performed on change in qMEP metrics. Results: Expanded Disability Status Scale and ambulation score progressed in the rANOVA model (p < 0.05; post-hoc comparison baseline-year 2, p < 0.1). Lower limb and combined qMEP scores showed significant deterioration of latency (p < 0.01, MEP-LL_CxM-sh: p < 0.05) and in post-hoc comparisons (baseline-year 2, p < 0.05), qMEP_CxM-mn even over 1 year (p < 0.05). Effect sizes were higher for qMEP scores than for clinical measures, and slightly but consistently higher when based on CxM-mn compared to CxM-sh or CMCT. Subgroup analysis yielded no indication of higher sensitivity of timed clinical measures over qMEP scores. Two independent factors were detected, the first mainly associated with qMEP-LL, the second with qMEP-UL, explaining 65 and 29% of total variability, respectively. Conclusions: Deterioration in qMEP scores occurs earlier than EDSS progression in patients with PPMS. Upper and lower limb qMEP scores contribute independently to measuring change, and qMEP scores based on mean CxM are advantageous. The capability to detect subclinical changes longitudinally is a unique property of EP and complementary to clinical assessment. These features underline the role of EP as candidate biomarkers to measure effects of therapeutic interventions in PPMS.
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BACKGROUND: Motor and sensory evoked potentials (EP) are potential candidate biomarkers for clinical trials in multiple sclerosis. OBJECTIVE: To determine test -retest reliability of motor EP (MEP) and sensory EP (SEP) and associated EP-scores in patients with multiple sclerosis. METHODS: In three centres, 16 relapsing and five progressive multiple sclerosis patients had MEPs and SEPs 1-29 days apart. Five neurophysiologists independently marked latencies by central reading. By variance component analysis, we estimated the critical difference (absolute reliability) for cross-sectional group comparison, comparison of longitudinal group changes, within-subject minimal detectable change and defined within-subject improvement. RESULTS: Cortical SEP responses and cortico-muscular MEP latencies were more reliable than central conduction times. For comparison of 20 subjects per arm, cross-sectional group difference ranged from 0.7 to 3.9 ms and 1.1 to 1.7, group difference in longitudinal changes from 0.4 to 1.8 ms and 0.36 to 0.62, within-subject minimal detectable change from 1.2 to 5.8 ms and 1.2 to 2.0, within-subject improvement from 0.8 to 3.8ms and 0.8 to 1.3, for single EP modalities and EP scores, respectively. CONCLUSIONS: Multicentre EP assessment with central EP reading is feasible and reliable. The critical difference is reasonably low to detect significant group changes and to define responders. The results support the concept of using EP and EP-scores as candidate response biomarkers for quantification of disease progression and for studying remyelination in multiple sclerosis.
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OBJECTIVE: To study if the thalamic lateral geniculate nucleus (LGN) is affected in multiple sclerosis (MS) due to anterograde degeneration from optic neuritis (ON) or retrograde degeneration from optic radiation (OR) pathology, and if this is relevant for visual function. METHODS: In this cross-sectional study, LGN volume of 34 patients with relapsing-remitting MS and 33 matched healthy controls (HC) was assessed on MRI using atlas-based automated segmentation (MAGeT). ON history, thickness of the ganglion cell-inner plexiform layer (GC-IPL), OR lesion volume, and fractional anisotropy (FA) of normal-appearing OR (NAOR-FA) were assessed as measures of afferent visual pathway damage. Visual function was tested, including low-contrast letter acuity (LCLA) and Hardy-Rand-Rittler (HRR) plates for color vision. RESULTS: LGN volume was reduced in patients vs HC (165.5 ± 45.5 vs 191.4 ± 47.7 mm3, B = -25.89, SE = 5.83, p < 0.001). It was associated with GC-IPL thickness (B = 0.95, SE = 0.33, p = 0.006) and correlated with OR lesion volume (Spearman ρ = -0.53, p = 0.001), and these relationships remained after adjustment for normalized brain volume. There was no association between NAOR-FA and LGN volume (B = -133.28, SE = 88.47, p = 0.137). LGN volume was not associated with LCLA (B = 5.5 × 10-5, SE = 0.03, p = 0.998), but it correlated with HRR color vision (ρ = 0.39, p = 0.032). CONCLUSIONS: LGN volume loss in MS indicates structural damage with potential functional relevance. Our results suggest both anterograde degeneration from the retina and retrograde degeneration from the OR lesions as underlying causes. LGN volume is a promising marker reflecting damage of the visual pathway in MS, with the advantage of individual measurement per patient on conventional MRI.
Assuntos
Corpos Geniculados/patologia , Esclerose Múltipla/patologia , Degeneração Neural/patologia , Vias Visuais/patologia , Adulto , Estudos Transversais , Feminino , Corpos Geniculados/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla/diagnóstico por imagem , Degeneração Neural/diagnóstico por imagem , Testes Visuais , Visão Ocular/fisiologia , Vias Visuais/diagnóstico por imagemRESUMO
Evoked potentials (EP) characterize signal conduction in selected tracts of the central nervous system in a quantifiable way. Since alteration of signal conduction is the main mechanism of symptoms and signs in multiple sclerosis (MS), multimodal EP may serve as a representative measure of the functional impairment in MS. Moreover, EP have been shown to be predictive for disease course, and thus might help to select patient groups at high risk of progression for clinical trials. EP can detect deterioration, as well as improvement of impulse propagation, independently from the mechanism causing the change. Therefore, they are candidates for biomarkers with application in clinical phase-II trials. Applicability of EP in multicenter trials has been limited by different standards of registration and assessment.
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Biomarcadores , Potenciais Evocados , Esclerose Múltipla/diagnóstico , Humanos , Esclerose Múltipla/fisiopatologiaRESUMO
Evoked potentials (EPs) are a powerful and cost-effective tool for evaluating the integrity and function of the central nervous system. Although imaging techniques, such as MRI, have recently become increasingly important in the diagnosis of neurological diseases, over the past 30 years, many neurologists have continued to employ EPs in specific clinical applications. This review presents an overview of the recent evolution of 'classical' clinical applications of EPs in terms of early diagnosis and disease monitoring and is an extension of a previous review published in this journal in 2005 by Walsh and collaborators. We also provide an update on emerging EPs based on gustatory, olfactory and pain stimulation that may be used as clinically relevant markers of neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and cortical or peripheral impaired pain perception. EPs based on multichannel electroencephalography recordings, known as high-density EPs, help to better differentiate between healthy subjects and patients and, moreover, they provide valuable spatial information regarding the site of the lesion. EPs are reliable disease-progression biomarkers of several neurological diseases, such as multiple sclerosis and other demyelinating disorders. Overall, EPs are excellent neurophysiological tools that will expand standard clinical practice in modern neurology.
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Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/fisiopatologia , Eletroencefalografia/métodos , Potenciais Evocados/fisiologia , Encéfalo/fisiopatologia , Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/fisiopatologia , Progressão da Doença , Diagnóstico Precoce , Humanos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/fisiopatologia , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/fisiopatologia , Exame Neurológico , Percepção da Dor/fisiologia , Nervos Periféricos/fisiopatologia , Valores de Referência , Olfato/fisiologia , Paladar/fisiologiaRESUMO
Spontaneous fluctuations of neuronal activity in large-scale distributed networks are a hallmark of the resting brain. In relapsing-remitting multiple sclerosis (RRMS) several fMRI studies have suggested altered resting-state connectivity patterns. Topographical EEG analysis reveals much faster temporal fluctuations in the tens of milliseconds time range (termed "microstates"), which showed altered properties in a number of neuropsychiatric conditions. We investigated whether these microstates were altered in patients with RRMS, and if the microstates' temporal properties reflected a link to the patients' clinical features. We acquired 256-channel EEG in 53 patients (mean age 37.6 years, 45 females, mean disease duration 9.99 years, Expanded Disability Status Scale ≤ 4, mean 2.2) and 49 healthy controls (mean age 36.4 years, 33 females). We analyzed segments of a total of 5 min of EEG during resting wakefulness and determined for both groups the four predominant microstates using established clustering methods. We found significant differences in the temporal dynamics of two of the four microstates between healthy controls and patients with RRMS in terms of increased appearance and prolonged duration. Using stepwise multiple linear regression models with 8-fold cross-validation, we found evidence that these electrophysiological measures predicted a patient's total disease duration, annual relapse rate, disability score, as well as depression score, and cognitive fatigue measure. In RRMS patients, microstate analysis captured altered fluctuations of EEG topographies in the sub-second range. This measure of high temporal resolution provided potentially powerful markers of disease activity and neuropsychiatric co-morbidities in RRMS.
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Mapeamento Encefálico , Ondas Encefálicas/fisiologia , Eletroencefalografia , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Adulto , Feminino , Humanos , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Oxigênio/sangue , Valor Preditivo dos Testes , Escalas de Graduação PsiquiátricaRESUMO
Connectivity analysis characterizes normal and altered brain function, for example, using the phase lag index (PLI), which is based on phase relations. However, reliability of PLI over time is limited, especially for single- or regional-link analysis. One possible cause is repeated changes of network configuration during registration. These network changes may be associated with changes of the surface potential fields, which can be characterized by microstate analysis. Microstate analysis describes repeating periods of quasistable surface potential fields lasting in the subsecond time range. This study aims to describe a novel combination of PLI with microstate analysis (microstate-segmented PLI = msPLI) and to determine its impact on the reliability of single links, regional links, and derived graph measures. msPLI was calculated in a cohort of 34 healthy controls three times over 2 years. A fully automated processing of electroencephalography was used. Resulting connectomes were compared using Pearson correlation, and test-retest reliability (TRT reliability) was assessed using the intraclass correlation coefficient. msPLI resulted in higher TRT reliability than classical PLI analysis for single or regional links, average clustering coefficient, average shortest path length, and degree diversity. Combination of microstates and phase-derived connectivity measures such as PLI improves reliability of single-link, regional-link, and graph analysis.
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Córtex Cerebral/fisiologia , Conectoma/métodos , Eletroencefalografia/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Processamento de Sinais Assistido por Computador , Adulto JovemRESUMO
Cognitive decline is common with the progression of Parkinson's disease (PD). Different candidate biomarkers are currently studied for the risk of dementia in PD. Several studies have shown that quantitative EEG (QEEG) is a promising predictor of PD-related cognitive decline. In this paper we briefly outline the basics of QEEG analysis and analyze the recent publications addressing the predictive value of QEEG in the context of cognitive decline in PD. The MEDLINE database was searched for relevant publications from January 01, 2005, to March 02, 2015. Twenty-four studies reported QEEG findings in various cognitive states in PD. Spectral and connectivity markers of QEEG could help to discriminate between PD patients with different level of cognitive decline. QEEG variables correlate with tools for cognitive assessment over time and are associated with significant hazard ratios to predict PD-related dementia. QEEG analysis shows high test-retest reliability and avoids learning effects associated with some neuropsychological testing; it is noninvasive and relatively easy to repeat.
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OBJECTIVE: To compare the ability of different evoked potential scores (EPS) to monitor and predict the disease course in multiple sclerosis (MS). METHODS: Seventy-two patients with MS or clinically isolated syndrome were investigated by visual, motor, and somatosensory EP and expanded disability status scale (EDSS) at baseline (T0) and months 6, 12, 24, 36 (T4). EP results were rated according to ordinal (o), semi-quantitative (sq), and quantitative (q) EPS. Spearman rank correlation and multivariable linear regression were used to investigate the associations between EPS and clinical disability. RESULTS: All EPS correlated with EDSS cross-sectionally (0.72⩽rho⩽0.87, all p<0.001) and longitudinally (0.39⩽rho⩽0.47, all p⩽0.004). EPS(T0) and EDSS(T0) together explained 85-86% of EDSS(T4) variance. A posteriori power calculation showed that the sample sizes needed to detect significant changes over 6 months in q-EPS, sq-EPS and o-EPS with 90% certainty would be 50, 129 and 222, respectively. q-EPS change(T1-T0) correlated with EDSS change(T4-T0) (rho=0.56, p<0.001), while sq-EPS and o-EPS changes(T1-T0) did not. CONCLUSION: All three EPS allow disease course monitoring in MS. However, the quantitative EPS detects clinically relevant short-term changes with a smaller sample size than semi-quantitative or ordinal EPS. SIGNIFICANCE: These results underscore the potential of EPS to characterize MS disease evolution.
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Potencial Evocado Motor/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Potenciais Evocados Visuais/fisiologia , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/fisiopatologia , Índice de Gravidade de Doença , Adulto , Estudos de Coortes , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Cognitive deficits in Parkinson's disease (PD) are heterogeneous and can be classified into cognitive domains. Quantitative EEG is related to and predictive of cognitive status in PD. In this cross-sectional study, the relationship of cognitive domains and EEG slowing in PD patients without dementia is investigated. METHODS: A total of 48 patients with idiopathic PD were neuropsychologically tested. Cognitive domain scores were calculated combining Z-scores of test variables. Slowing of EEG was measured with median EEG frequency. Linear regression was used for correlational analyses and to control for confounding factors. RESULTS: EEG median frequency was significantly correlated to cognitive performance in most domains (episodic long-term memory, rho = 0.54; overall cognitive score, rho = 0.47; fluency, rho = 0.39; attention, rho = 0.37; executive function, rho = 0.34), but not to visuospatial functions and working memory. CONCLUSION: Global EEG slowing is a marker for overall cognitive impairment in PD and correlates with impairment in the domains attention, executive function, verbal fluency, and episodic long-term memory, but not with working memory and visuospatial functions. These disparate effects warrant further investigations.
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Transtornos Cognitivos/etiologia , Disfunção Cognitiva/etiologia , Eletroencefalografia , Doença de Parkinson/psicologia , Idoso , Cognição/classificação , Transtornos Cognitivos/diagnóstico , Disfunção Cognitiva/diagnóstico , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
INTRODUCTION: Electroencephalography (EEG) microstates and brain network are altered in patients with Alzheimer's disease (AD) and discussed as potential biomarkers for AD. Microstates correspond to defined states of brain activity, and their connectivity patterns may change accordingly. Little is known about alteration of connectivity in microstates, especially in patients with amnestic mild cognitive impairment with stable or improving cognition within 30 months (aMCI). METHODS: Thirty-five outpatients with aMCI or mild dementia (mean age 77 ± 7 years, 47% male, Mini Mental State Examination score ≥24) had comprehensive neuropsychological and clinical examinations. Subjects with cognitive decline over 30 months were allocated to the AD group, subjects with stable or improving cognition to the MCI-stable group. Results of neuropsychological testing at baseline were summarized in six domain scores. Resting state EEG was recorded with 256 electrodes and analyzed using TAPEEG. Five microstates were defined and individual data fitted. After phase transformation, the phase lag index (PLI) was calculated for the five microstates in every subject. Networks were reduced to 22 nodes for statistical analysis. RESULTS: The domain score for verbal learning and memory and the microstate segmented PLI between the left centro-lateral and parieto-occipital regions in the theta band at baseline differentiated significantly between the groups. In the present sample, they separated in a logistic regression model with a 100% positive predictive value, 60% negative predictive value, 100% specificity and 77% sensitivity between AD and MCI-stable. CONCLUSIONS: Combining neuropsychological and quantitative EEG test results allows differentiation between subjects with aMCI remaining stable and subjects with aMCI deteriorating over 30 months.
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Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Encéfalo/fisiopatologia , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico , Testes Neuropsicológicos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Disfunção Cognitiva/fisiopatologia , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Memória/fisiologiaRESUMO
OBJECTIVE: Mild cognitive impairment in Parkinson's disease (PD-MCI) is diagnosed based on the results of a standardized set of cognitive tests. We investigate whether quantitative EEG (qEEG) measures could identify differences between cognitively normal PD (PD-CogNL) and PD-MCI patients. METHODS: High-resolution EEG was recorded in 53 patients with Parkinson's disease (PD). Relative power in five frequency bands was calculated globally and for ten regions. Peak and median frequencies were determined. qEEG results were compared between groups. Effect sizes of all variables were calculated. The best separating variable was used to demonstrate subject-wise classification. RESULTS: Lower mean values were observed in global alpha1 power and alpha1 power in five brain regions (left hemisphere: frontal, central, temporal, occipital; right hemisphere: temporal, P < 0.05), differentiating between PD-CogNL and PD-MCI groups. Effect sizes were high, ranging from 0.79 to 0.87. Median frequency was 8.56 ± 0.74 Hz and was not different between the groups. The variable with the best subject-wise classification was the power in the alpha1 band in the right temporal region. The area under the corresponding receiver operating characteristic (ROC) curve was 0.72. The optimal classification threshold yielded a sensitivity of 65.9% and a specificity of 66.7%. The positive and negative predictive values were 87.1% and 36.4%, respectively. INTERPRETATION: Reduction in alpha1 band power in nondemented PD patients, particularly in the right temporal region, is highly indicative of MCI in PD patients. The results might be used to assist in time-efficient diagnosis of PD-MCI and avoid the drawbacks of test-retest effect in repeated neuropsychological testing.
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BACKGROUND: Slowing of the electroencephalogram (EEG) is frequent in Parkinson's (PD) and Alzheimer's disease (AD) and correlates with cognitive decline. As overlap pathology plays a role in the pathogenesis of dementia, it is likely that demented patients in PD show similar physiological alterations as in AD. OBJECTIVE: To analyze distinctive quantitative EEG characteristics in early cognitive dysfunction in PD and AD. METHODS: Forty patients (20 PD- and 20 AD patients with early cognitive impairment) and 20 normal controls (NC) were matched for gender, age, and education. Resting state EEG was recorded from 256 electrodes. Relative power spectra, median frequency (4-14 Hz), and neuropsychological outcome were compared between groups. RESULTS: Relative theta power in left temporal region and median frequency separated the three groups significantly (p = 0.002 and p < 0.001). Relative theta power was increased and median frequency reduced in patients with both diseases compared to NC. Median frequency was higher in AD than in PD and classified groups significantly (p = 0.02). CONCLUSION: Increase of theta power in the left temporal region and a reduction of median frequency were associated with presence of AD or PD. PD patients are characterized by a pronounced slowing as compared to AD patients. Therefore, in both disorders EEG slowing might be a useful biomarker for beginning cognitive decline.
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Functional connectivity (FC) and graph measures provide powerful means to analyze complex networks. The current study determines the inter-subject-variability using the coefficient of variation (CoV) and long-term test-retest-reliability (TRT) using the intra-class correlation coefficient (ICC) in 44 healthy subjects with 35 having a follow-up at years 1 and 2. FC was estimated from 256-channel-EEG by the phase-lag-index (PLI) and weighted PLI (wPLI) during an eyes-closed resting state condition. PLI quantifies the asymmetry of the distribution of instantaneous phase differences of two time-series and signifies, whether a consistent non-zero phase lag exists. WPLI extends the PLI by additionally accounting for the magnitude of the phase difference. Signal-space global and regional PLI/wPLI and weighted first-order graph measures, i.e. normalized clustering coefficient (gamma), normalized average path length (lambda), and the small-world-index (SWI) were calculated for theta-, alpha1-, alpha2- and beta-frequency bands. Inter-subject variability of global PLI was low to moderate over frequency bands (0.12Assuntos
Eletroencefalografia
, Rede Nervosa/fisiologia
, Adulto
, Feminino
, Humanos
, Masculino
, Pessoa de Meia-Idade
, Reprodutibilidade dos Testes
, Fatores de Tempo
, Adulto Jovem