Publications by authors named "R H Reijntjes"

27 Publications

The prevalence of pain in Huntington's disease in a large worldwide cohort.

Parkinsonism Relat Disord 2021 Jun 19;89:73-78. Epub 2021 Jun 19.

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

Introduction: Pain could be an unknown non-motor symptom in Huntington's Disease (HD). The aim is therefore, to study the prevalence of pain interference, painful conditions and analgesic use across the different stages of HD and compare these levels to non-HD gene mutation carriers.

Methods: A cross-sectional analysis of the Enroll-HD study was conducted in premanifest, manifest HD gene mutation carriers (n = 3989 and n = 7,485, respectively) and in non-HD gene mutation carriers (n = 3719). To investigate group differences, multivariable logistic regression analysis was performed with pairwise comparisons.

Results: In the HD mutation carriers, the overall prevalence of pain interference was 34% (95% CI 31%-35%), of painful conditions 17% (95% CI 15%-19%) and analgesic use 13% (95% CI 11%-15%). Compared to non-mutation carriers, the prevalence of pain interference was significantly higher in the middle stage of HD (33% [95% CI 31%-35%] vs 42% [95% CI 39%-45%], P = 0,02), whereas the prevalence of painful conditions was significant lower in the late and middle stage of HD (17% [95% CI 16%-18%] vs 12% [95% CI 10%-14%], 15% [95% CI 13%-17%], P < 0,01]. No significant group difference was present in analgesic use.

Conclusions: The prevalence of pain interference increases as HD progresses, however, the prevalence of painful conditions and analgesics do not increase accordingly. Further studies are necessary to investigate the aetiology of pain in HD and the risk for undertreatment of pain.
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http://dx.doi.org/10.1016/j.parkreldis.2021.06.015DOI Listing
June 2021

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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http://dx.doi.org/10.1002/acn3.51412DOI Listing
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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http://dx.doi.org/10.1016/j.clinph.2021.04.013DOI Listing
August 2021

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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http://dx.doi.org/10.1161/CIRCRESAHA.120.316662DOI Listing
August 2020

Progressive microstructural changes of the occipital cortex in Huntington's disease.

Brain Imaging Behav 2018 Dec;12(6):1786-1794

Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands.

In this study we longitudinally investigated the rate of microstructural alterations in the occipital cortex in different stages of Huntington's disease (HD) by applying an automated atlas-based approach to diffusion MRI data. Twenty-two premanifest (preHD), 10 early manifest HD (early HD) and 24 healthy control subjects completed baseline and two year follow-up scans. The preHD group was stratified based on the predicted years to disease onset into a far (preHD-A) and near (preHD-B) to disease onset group. Clinical and behavioral measures were collected per assessment time point. An automated atlas-based DTI analysis approach was used to obtain the mean, axial and radial diffusivities of the occipital cortex. We found that the longitudinal rate of diffusivity change in the superior occipital gyrus (SOG), middle occipital gyrus (MOG), and inferior occipital gyrus (IOG) was significantly higher in early HD compared to both preHD and controls (all p's ≤ 0.005), which can be interpreted as an increased rate of microstructural degeneration. Furthermore, the change rate in the diffusivity of the MOG could significantly discriminate between preHD-B compared to preHD-A and the other groups (all p's ≤ 0.04). Finally, we found an inverse correlation between the Stroop Word Reading task and diffusivities in the SOG and MOG (all p's ≤ 0.01). These findings suggest that measures obtained from the occipital cortex can serve as sensitive longitudinal biomarkers for disease progression in preHD-B and early HD. These could in turn be used to assess potential effects of proposed disease modifying therapies.
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http://dx.doi.org/10.1007/s11682-018-9849-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302057PMC
December 2018
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