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Background: Viral meningitis/encephalitis (ME) is a rare but potentially harmful disease. The prompt identification of the respective virus is important to guide not only treatment but also potential public health countermeasures. However, in about 40% of cases, no virus is identified despite an extensive diagnostic workup. The aim of the present study was to analyze demographic, seasonal, and routine cerebrospinal fluid (CSF) parameters in cases of viral ME and assess their utility for the prediction of the causative virus. Methods: Demographic data, season, and routine CSF parameters (total leucocytes, CSF cell differentiation, age-adjusted CSF/serum albumin ratio, and total immunoglobulin ratios) were retrospectively assessed in cases of viral ME. Results: In total, 156 cases of acute viral ME (74 female, median age 40.0 years) were treated at a tertiary-care hospital in Germany. Specific viral infections were detected in 93 (59.6%) cases. Of these, 14 (9.0%) cases were caused by herpes simplex virus (HSV), 36 (23.1%) by varicella-zoster virus (VZV), 27 (17.3%) by enteroviruses, 9 (5.8%) by West Nile virus (WNV), and 7 (4.5%) by other specific viruses. Additionally, 64 (41.0%) cases of ME of unknown viral etiology were diagnosed. Cases of WNV ME were older, predominantly male, showed a severe disruption of the blood–CSF–barrier, a high proportion of neutrophils in CSF, and an intrathecal total immunoglobulin M synthesis in the first CSF sample. In a multinominal logistic regression analysis, the accuracy of these CSF parameters together with age and seasonality was best for the prediction of WNV (87.5%), followed by unknown viral etiology (66.7%), VZV (61.8%), and enteroviruses (51.9%). Conclusions: Cases with WNV ME showed a specific pattern of routine CSF parameters and demographic data that allowed for their identification with good accuracy. These findings might help to guide the diagnostic workup in cases with viral ME, in particular allowing the timely identification of cases with ME due to WNV. [ABSTRACT FROM AUTHOR]

Bradykinesia is a cardinal motor symptom in Parkinson's disease (PD), the pathophysiology of which is not fully understood. We analyzed the role of cross-frequency coupling of oscillatory cortical activity in motor impairment in patients with PD and healthy controls. High-density EEG signals were recorded during various motor activities and at rest. Patients performed a repetitive finger-pressing task normally, but were slower than controls during tapping. Phase-amplitude coupling (PAC) between b (13-30 Hz) and broadband c (50-150 Hz) was computed from individual EEG source signals in the premotor, primary motor, and primary somatosensory cortices, and the primary somatosensory complex. In all four regions, averaging the entire movement period resulted in higher PAC in patients than in controls for the resting condition and the pressing task (similar performance between groups). However, this was not the case for the tapping tasks where patients performed slower. This suggests the strength of state-related b-c PAC does not determine Parkinsonian bradykinesia. Examination of the dynamics of oscillatory EEG signals during motor transitions revealed a distinctive motif of PAC rise and decay around press onset. This pattern was also present at press offset and slow tapping onset, linking such idiosyncratic PAC changes to transitions between different movement states. The transition-related PAC modulation in patients was similar to controls in the pressing task but flattened during slow tapping, which related to normal and abnormal performance, respectively. These findings suggest that the dysfunctional evolution of neuronal population dynamics during movement execution is an important component of the pathophysiology of Parkinsonian bradykinesia. NEW & NOTEWORTHY Our findings using noninvasive EEG recordings provide evidence that PAC dynamics might play a role in the physiological cortical control of movement execution and may encode transitions between movement states. Results in patients with Parkinson's disease suggest that bradykinesia is related to a deficit of the dynamic regulation of PAC during movement execution rather than its absolute strength. Our findings may contribute to the development of a new concept of the pathophysiology of bradykinesia. [ABSTRACT FROM AUTHOR]

Abnormal phase-amplitude coupling between β and broadband-γ activities has been identified in recordings from the cortex or scalp of patients with Parkinson's disease. While enhanced phase-amplitude coupling has been proposed as a biomarker of Parkinson's disease, the neuronal mechanisms underlying the abnormal coupling and its relationship to motor impairments in Parkinson's disease remain unclear. To address these issues, we performed an in-depth analysis of high-density EEG recordings at rest in 19 patients with Parkinson's disease and 20 age- and sex-matched healthy control subjects. EEG signals were projected onto the individual cortical surfaces using source reconstruction techniques and separated into spatiotemporal components using independent component analysis. Compared to healthy controls, phase-amplitude coupling of Parkinson's disease patients was enhanced in dorsolateral prefrontal cortex, premotor cortex, primary motor cortex and somatosensory cortex, the difference being statistically significant in the hemisphere contralateral to the clinically more affected side. β and γ signals involved in generating abnormal phase-amplitude coupling were not strictly phase-phase coupled, ruling out that phase-amplitude coupling merely reflects the abnormal activity of a single oscillator in a recurrent network. We found important differences for couplings between the β and γ signals from identical components as opposed to those from different components (originating from distinct spatial locations). While both couplings were abnormally enhanced in patients, only the latter were correlated with clinical motor severity as indexed by part III of the Movement Disorder Society Unified Parkinson's Disease Rating Scale. Correlations with parkinsonian motor symptoms of such inter-component couplings were found in premotor, primary motor and somatosensory cortex, but not in dorsolateral prefrontal cortex, suggesting motor domain specificity. The topography of phase-amplitude coupling demonstrated profound differences in patients compared to controls. These findings suggest, first, that enhanced phase-amplitude coupling in Parkinson's disease patients originates from the coupling between distinct neural networks in several brain regions involved in motor control. Because these regions included the somatosensory cortex, abnormal phase-amplitude coupling is not exclusively tied to the hyperdirect tract connecting cortical regions monosynaptically with the subthalamic nucleus. Second, only the coupling between β and γ signals from different components appears to have pathophysiological significance, suggesting that therapeutic approaches breaking the abnormal lateral coupling between neuronal circuits may be more promising than targeting phase-amplitude coupling per se. [ABSTRACT FROM AUTHOR]

Abnormal phase-amplitude coupling between β and broadband-γ activities has been identified in recordings from the cortex or scalp of patients with Parkinson's disease. While enhanced phase-amplitude coupling has been proposed as a biomarker of Parkinson's disease, the neuronal mechanisms underlying the abnormal coupling and its relationship to motor impairments in Parkinson's disease remain unclear. To address these issues, we performed an in-depth analysis of high-density EEG recordings at rest in 19 patients with Parkinson's disease and 20 age- and sex-matched healthy control subjects. EEG signals were projected onto the individual cortical surfaces using source reconstruction techniques and separated into spatiotemporal components using independent component analysis. Compared to healthy controls, phase-amplitude coupling of Parkinson's disease patients was enhanced in dorsolateral prefrontal cortex, premotor cortex, primary motor cortex and somatosensory cortex, the difference being statistically significant in the hemisphere contralateral to the clinically more affected side. β and γ signals involved in generating abnormal phase-amplitude coupling were not strictly phase-phase coupled, ruling out that phase-amplitude coupling merely reflects the abnormal activity of a single oscillator in a recurrent network. We found important differences for couplings between the β and γ signals from identical components as opposed to those from different components (originating from distinct spatial locations). While both couplings were abnormally enhanced in patients, only the latter were correlated with clinical motor severity as indexed by part III of the Movement Disorder Society Unified Parkinson's Disease Rating Scale. Correlations with parkinsonian motor symptoms of such inter-component couplings were found in premotor, primary motor and somatosensory cortex, but not in dorsolateral prefrontal cortex, suggesting motor domain specificity. The topography of phase-amplitude coupling demonstrated profound differences in patients compared to controls. These findings suggest, first, that enhanced phase-amplitude coupling in Parkinson's disease patients originates from the coupling between distinct neural networks in several brain regions involved in motor control. Because these regions included the somatosensory cortex, abnormal phase-amplitude coupling is not exclusively tied to the hyperdirect tract connecting cortical regions monosynaptically with the subthalamic nucleus. Second, only the coupling between β and γ signals from different components appears to have pathophysiological significance, suggesting that therapeutic approaches breaking the abnormal lateral coupling between neuronal circuits may be more promising than targeting phase-amplitude coupling per se., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)