Publications by authors named "F I Kerkhof"

19 Publications

New hemodynamic criteria to separate classical orthostatic hypotension from vasovagal syncope.

Ann Clin Transl Neurol 2021 Jun 24. Epub 2021 Jun 24.

Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.

Objective: To define and evaluate hemodynamic criteria to distinguish between classical orthostatic hypotension (cOH) and vasovagal syncope (VVS) in tilt table testing (TTT).

Methods: Inclusion criteria for VVS were a history of VVS and tilt-induced syncope defined as a blood pressure (BP) decrease and electroencephalographic changes during syncope with complaint recognition. Criteria for cOH were a history of cOH and a BP decrease meeting published criteria. Clinical diagnoses were established prior to TTT. We assessed (1) whether the decrease of systolic BP accelerated, "convex," or decelerated, "concave"; (2) the time from head-up tilt to when BP reached one-half its maximal decrease; (3) the difference between baseline heart rate (HR) and HR at BP nadir. We calculated the diagnostic yield of optimized thresholds of these features and their combinations.

Results: We included 82 VVS cases (40% men, median age 44 years) and 65 cOH cases (66% men, median age 70 years). BP decrease was concave in cOH in 79% and convex in VVS in 94% (p < 0.001). The time to reach half the BP decrease was shorter in cOH (median 34 sec, interquartile range (IQR) 19-98 sec) than in VVS (median 1571 sec, IQR 1381-1775 sec, p < 0.001). Mean HR increased by 11 ± 11 bpm in cOH and decreased by 20 ± 19 bpm in VVS (p < 0.001). When all three features pointed to VVS, sensitivity for VVS was 82% and specificity was 100%. When all three pointed to cOH, sensitivity for cOH was 71% and specificity was 100%.

Interpretation: These new hemodynamic criteria reliably differentiate cOH from VVS.
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June 2021

Deriving reference values for nerve conduction studies from existing data using mixture model clustering.

Clin Neurophysiol 2021 Aug 21;132(8):1820-1829. Epub 2021 May 21.

Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address:

Objective: to obtain locally valid reference values (RVs) from existing nerve conduction study (NCS) data.

Methods: we used age, sex, height and limb temperature-based mixture model clustering (MMC) to identify normal and abnormal measurements on NCS data from two university hospitals. We compared MMC-derived RVs to published data; examined the effect of using different variables; validated MMC-derived RVs using independent data from 26 healthy control subjects and investigated their clinical applicability for the diagnosis of polyneuropathy.

Results: MMC-derived RVs were similar to published RVs. Clustering can be achieved using only sex and age as variables. MMC is likely to yield reliable results with fewer abnormal than normal measurements and when the total number of measurements is at least 300. Measurements from healthy controls fell within the 95% MMC-derived prediction interval in 97.4% of cases.

Conclusions: MMC can be used to obtain RVs from existing data, providing a locally valid, accurate reflection of the (ab)normality of an NCS result.

Significance: MMC can be used to generate locally valid RVs for any test for which sufficient data are available..
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August 2021

Measuring CMAPs in addition to MEPs can distinguish peripheral ischemia from spinal cord ischemia during endovascular aortic repair.

Clin Neurophysiol Pract 2021 11;6:16-21. Epub 2020 Dec 11.

Department of Neurology, Leiden University Medical Center, the Netherlands.

Objective: Spinal cord injury is a devastating complication after endovascular thoracic and thoracoabdominal aneurysm repair (EVAR). Motor evoked potentials (MEPs) can be monitored to detect spinal cord injury, but may also be affected by peripheral ischemia caused by femoral artery sheaths. We aimed to determine the incidence of peripheral ischemia during EVAR, and whether central and peripheral ischemia can be distinguished using compound muscle action potentials (CMAPs).

Methods: We retrospectively analyzed all EVAR procedures between March 1st 2015 and January 1st 2020 during which MEPs were monitored. Peripheral ischemia was defined as both a reduction in MEP amplitudes reversed by removing the femoral sheaths and no clinical signs of immediate post-procedural paraparesis. All other MEP decreases were defined as central ischemia.

Results: A significant MEP decrease occurred in 14/27 (52%) of all procedures. Simultaneous CMAP amplitude reduction was observed in 7/8 (88%) of procedures where peripheral ischemia occurred, and never in procedures with central ischemia.

Conclusions: MEP reductions due to peripheral ischemia are common during EVAR. A MEP-reduction without a CMAP decrease indicates central ischemia.

Significance: CMAP measurements can help to distinguish central from peripheral ischemia, potentially reducing the chance of misinterpreting of MEP amplitude declines as centrally mediated, without affecting sensitivity.
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December 2020

Novel Methods for Quantification of Vasodepression and Cardioinhibition During Tilt-Induced Vasovagal Syncope.

Circ Res 2020 08 28;127(5):e126-e138. Epub 2020 May 28.

Cardiovascular Division, Arrhythmia Center, Department of Medicine, University of Minnesota, Minneapolis (D.G.B.).

Rationale: Assessing the relative contributions of cardioinhibition and vasodepression to the blood pressure (BP) decrease in tilt-induced vasovagal syncope requires methods that reflect BP physiology accurately.

Objective: To assess the relative contributions of cardioinhibition and vasodepression to tilt-induced vasovagal syncope using novel methods.

Methods And Results: We studied the parameters determining BP, that is, stroke volume (SV), heart rate (HR), and total peripheral resistance (TPR), in 163 patients with tilt-induced vasovagal syncope documented by continuous ECG and video EEG monitoring. We defined the beginning of cardioinhibition as the start of an HR decrease (HR) before syncope and used logarithms of SV, HR, and TPR ratios to quantify the multiplicative relation BP=SV·HR·TPR. We defined 3 stages before syncope and 2 after it based on direction changes of these parameters. The earliest BP decrease occurred 9 minutes before syncope. Cardioinhibition was observed in 91% of patients at a median time of 58 seconds before syncope. At that time, SV had a strong negative effect on BP, TPR a lesser negative effect, while HR had increased (all <0.001). At the onset of cardioinhibition, the median HR was at 98 bpm higher than baseline. Cardioinhibition thus initially only represented a reduction of the corrective HR increase but was nonetheless accompanied by an immediate acceleration of the ongoing BP decrease. At syncope, SV and HR contributed similarly to the BP decrease (<0.001), while TPR did not affect BP.

Conclusions: The novel methods allowed the relative effects of SV, HR, and TPR on BP to be assessed separately, although all act together. The 2 major factors lowering BP in tilt-induced vasovagal syncope were reduced SV and cardioinhibition. We suggest that the term vasodepression in reflex syncope should not be limited to reduced arterial vasoconstriction, reflected in TPR, but should also encompass venous pooling, reflected in SV.
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August 2020

The digital human forearm and hand.

J Anat 2018 11 17;233(5):557-566. Epub 2018 Sep 17.

Department of Development and Regeneration, KU Leuven Campus Kulak, Kortrijk, Belgium.

How changes in anatomy affect joint biomechanics can be studied using musculoskeletal modelling, making it a valuable tool to explore joint function in healthy and pathological joints. However, gathering the anatomical, geometrical and physiological data necessary to create a model can be challenging. Very few integrated datasets exist and even less raw data is openly available to create new models. Therefore, the goal of the present study is to create an integrated digital forearm and make the raw data available via an open-access database. An un-embalmed cadaveric arm was digitized using 7T MRI and CT scans. 3D geometrical models of bones, cartilage, muscle and muscle pathways were created. After MRI and CT scanning, physiological muscle parameters (e.g. muscle volume, mass, length, pennation angle, physiological cross-sectional area, tendon length) were obtained via detailed dissection. After dissection, muscle biopsies were fixated and confocal microscopy was used to visualize and measure sarcomere lengths. This study provides an integrated anatomical dataset on which complete and accurate musculoskeletal models of the hand can be based. By creating a 3D digital human forearm, including all relevant anatomical parameters, a more realistic musculoskeletal model can be created. Furthermore, open access to the anatomical dataset makes it possible for other researchers to use these data in the development of a musculoskeletal model of the hand.
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November 2018