Orthostatic stress response in pediatric Fontan patients and the effect of ACE inhibition.

BACKGROUND: Many cardiocirculatory mechanisms are involved in the adaptation to orthostatic stress. While these mechanisms may be impaired in Fontan patients. However, it is yet unclear how Fontan patients, who exhibit a critical fluid balance, respond to orthostatic stress. Angiotensin converting enzyme inhibitors are often prescribed to Fontan patients, but they may negatively influence orthostatic tolerance. Therefore, we evaluated the response to orthostatic stress in pediatric Fontan patients before and after treatment with enalapril. METHODS: Thirty-five Fontan patients (aged 14 years) with moderate-good systolic ventricular function without pre-existent enalapril treatment were included. Before and after a three-month enalapril treatment period, the hemodynamic response to head-up tilt test was evaluated by various parameters including cardiac index, blood pressure, cerebral blood flow, aortic stiffness and cardiac autonomous nervous activity. Thirty-four healthy subjects (aged 13 years) served as controls. RESULTS: Fontan patients had a decreased cerebral blood flow and increased aortic stiffness in the supine position compared to controls, while all other factors did not differ. Patients and controls showed a comparable response to head-up tilt test for most parameters. Twenty-seven patients completed the enalapril study with a mean dosage of 0.3±0.1mg/kg/day. Most parameters were unaffected by enalapril, only the percent decrease in cardiac index to tilt was higher after treatment, but the cardiac index during tilt was not lower (3.0L/min/m2 pre-enalapril versus 2.8L/min/m2 after treatment; P = 0.15). CONCLUSION: Pediatric Fontan patients adequately respond to orthostasis with maintenance of blood pressure and cerebral blood flow and sufficient autonomic response. Enalapril treatment did not alter the response. CLINICAL TRIAL INFORMATION: Scientific title: ACE inhibition in Fontan patients: its effect on body fluid regulation (sAFE-study). The Netherlands National Trial Register: Trail NL6415. Registered 2017-07-20. Trial information: https://www.trialregister.nl/trial/6415.

EEG may serve as a biomarker in Huntington's disease using machine learning automatic classification.

Reliable markers measuring disease progression in Huntington's disease (HD), before and after disease manifestation, may guide a therapy aimed at slowing or halting disease progression. Quantitative electroencephalography (qEEG) may provide a quantification method for possible (sub)cortical dysfunction occurring prior to or concomitant with motor or cognitive disturbances observed in HD. In this pilot study we construct an automatic classifier distinguishing healthy controls from HD gene carriers using qEEG and derive qEEG features that correlate with clinical markers known to change with disease progression in HD, with the aim of exploring biomarker potential. We included twenty-six HD gene carriers (49.7 ± 8.5 years) and 25 healthy controls (52.7 ± 8.7 years). EEG was recorded for three minutes with subjects at rest. An EEG index was created by applying statistical pattern recognition to a large set of EEG features, which was subsequently tested using 10-fold cross-validation. The index resulted in a continuous variable ranging from 0 to 1: a low value indicating a state close to normal and a high value pointing to HD. qEEG features that correlate specifically with commonly used clinical markers in HD research were derived. The classification index had a specificity of 83%, a sensitivity of 83% and an accuracy of 83%. The area under the curve of the receiver operator characteristic curve was 0.9. qEEG analysis on subsets of electrophysiological features resulted in two highly significant correlations with clinical scores. The results of this pilot study suggest that qEEG may serve as a biomarker in HD. The indices correlating with modalities changing with the progression of the disease may lead to tools based on qEEG that help monitor efficacy in intervention studies.

Assessment of human sleep depth is being de-standardized by recently advised EEG electrode locations.

Human sleep depth was traditionally assessed by scoring electro-encephalographic slow-wave amplitudes at the globally standardized C4-M1 electrode derivation. Since 2007, the American Association of Sleep Medicine (AASM) has accepted three additional derivations for the same purpose. These might well differ in slow wave amplitudes which would bias the scorings. Some derivations might also introduce large inter-individual variability. We compared mean and variability of slow wave amplitudes between six derivations including the four AASM ones. Slow wave amplitudes in those derivations were simultaneously measured using automated analysis in 29 patients. Each amplitude was divided by the average from the six derivations, thus removing shared factors such as age, gender and sleep depth while retaining factors that differ between the derivations such as caused by local skull characteristics, electrode distance and neuronal dipole orientation. The remaining inter-individual variability differed significantly and up to a factor of two between the AASM derivations. The amplitudes differed significantly and up to 60% between the AASM derivations, causing substantial scoring bias between centres using different derivations. The resulting de-standardization most likely affects any patient group because the amplitude differences were consistent over diagnoses, genders, and age. Derivation-dependent amplitude thresholds were proposed to reduce the scoring bias. However, it would be better to settle on just one derivation, for instance Cz-Oz or Fpz-Cz because these have lowest variability while matching the traditional C4-M1 amplitudes.

A DC attenuator allows common EEG equipment to record fullband EEG, and fits fullband EEG into standard European Data Format.

OBJECTIVE: Traditional electroencephalogram (EEG) recorders reject low frequencies and DC and therefore cannot handle fullband EEG. Dedicated fullband recorders use non-standard file formats, because the standard format (EDF) cannot handle large DC electrode offset voltages. Both facts limit the development and use of fullband EEG. We developed a modification that allows conventional equipment to record fullband EEG, and adapts both types of recorders to EDF. METHODS: The modification is a simple filter that attenuates the DC component and thus makes the EEG fit within traditional equipment limitations and EDF. The review software automatically 'de-attenuates' the DC component, without loss of information. RESULTS: DC attenuation by a factor of 10 made both types of recorders store DC attenuated fullband EEG into EDF files. Recordings were made during 0.5-24h in 46 subjects. The DC de-attenuator automatically reconstructed the original fullband EEG within an amplitude range of ±100mV and with a resolution of 0.3µV. Using sintered Ag-AgCl electrodes attached with common procedures, reconstructed DC EEG in spontaneously moving subjects ranged between ±32mV. CONCLUSIONS: The modification works. Fullband recordings can now be analyzed by independent software, archived and exchanged. SIGNIFICANCE: Any EEG system can be made to record fullband EEG into standard EDF.

Intraoperative nerve action and compound motor action potential recordings in patients with obstetric brachial plexus lesions.

OBJECT: A typical finding in supraclavicular exploration of infants with severe obstetric brachial plexus lesions (OBPLs) is a neuroma-in-continuity with the superior trunk and/or a root avulsion at C-5, C-6, or C-7. The operative strategy in these cases is determined by the intraoperative assessment of the severity of the lesion. Intraoperative nerve action potential (NAP) and evoked compound motor action potential (CMAP) recordings have been shown to be helpful diagnostic tools in adults, whereas their value in the intraoperative assessment of infants with OBPLs remains to be determined. METHODS: Intraoperative NAPs and CMAPs were systematically recorded from damaged and normal nerves of the upper brachial plexus in a consecutive series of 95 infants (mean age 175 days) with OBPLs. A total of 599 intraoperative NAP and 836 CMAP recordings were analyzed. The severity of the nerve lesions was graded as normal, axonotmesis, neurotmesis, or root avulsion, based on surgical, clinical, histological, and radiographic criteria. RESULTS: The correlation of NAP and CMAP recordings with the severity of the lesion was assessed. The specificity of an absent NAP or CMAP to predict a severe lesion (neurotmesis or avulsion) was > 0.9. However, the sensitivity of an absent NAP or CMAP for predicting a severe lesion was low (typically < 0.3). The severity of the nerve lesion was related to CMAP and NAP amplitudes. Cutoff points useful for intraoperative decision making could not be found to differentiate between lesion types in individual patients. CONCLUSIONS: Intraoperative NAP and CMAP recordings do not assist in decision making in the surgical treatment of infants with OBPLs. The authors' findings in infants cannot be generalized to adults.