Anouk van der Hoorn

Handedness correlates with the dominant parkinson side: A systematic review and meta-analysis

Parkinsons disease (PD) characteristically presents with asymmetrical symptoms, contralateral to the side of the most extensive cerebral affection. This intriguing asymmetry, even included in the definition for diagnosing PD, however, is still part of a mystery. The relation with handedness as a common indicator of cerebral asymmetry might provide a clue in the search for causal factors of asymmetrical symptom onset in PD. This possible relationship, however, is still under debate. The objective of this study was to establish whether a relation between handedness and dominant PD side exists. We searched for cross‐sectional or cohort studies that registered handedness and onset side in PD patients in PubMed, EMBASE, and Web of Science from their first record until 14 February 2011. Data about handedness and dominant PD side was extracted. Authors who registered both but not described their relation were contacted for further information. Odds ratios (ORs) were analyzed with a fixed effect Mantel‐Haenszel model. Heterogeneity and indications of publication bias were limited. Our electronic search identified 10 studies involving 4405 asymmetric PD patients. Of the right‐handed patients, 2413 (59.5%) had right‐dominant and 1644 (40.5%) had left‐dominant PD symptoms. For the left‐handed patients this relation was reversed, with 142 (40.8%) right‐dominant and 206 (59.2%) left‐dominant PD symptoms. Overall OR was 2.13 (95% confidence interval [CI], 1.71–2.66). Handedness and symptom dominance in PD are firmly related with each other in such a way that the PD symptoms emerge more often on the dominant hand‐side. Possible causal factors are discussed.

Handedness and dominant side of symptoms in Parkinson’s disease

The aim of this retrospective study was to assess the presence of a possible association between handedness and the side of symptom dominance in 963 patients with Parkinsons disease (PD). In only 287 patients the hand dominance was registered. Out of 254 right-handed patients, 158 (62%) had a right-side dominance of PD symptoms, while 96 patients (38%) had left-lateralized symptom dominance (p < 0.001). For the 33 left-handed subjects, 18 (55%) had left- and 15 (45%) had right-sided symptom dominance (p = 0.602). Right-handedness thus appeared to be associated with right-sided dominance of PD symptoms, while the group of left-handed patients was too small to draw conclusions from. Possible explanations are discussed.

Non-right-handedness and mental health problems among adolescents from the general population: The Trails Study.

To determine whether the association between non-right-handedness and mental problems among adolescents is specific for psychotic symptoms, we included a group of 2096 adolescents with a mean age of 14 years from the general population. Mental health problems were assessed using the parent, self-report, and teacher versions of the Child Behavior Checklist. Internalising problems comprised anxious and depressed, withdrawn and depressed, and somatic complaints. Externalising problems consisted of delinquent behaviour and aggressive behaviour. The remaining problems consisted of social problems, attention problems, and thought problems. The latter were divided into psychotic and non-psychotic items. A total of 14.3% of the adolescents were non-right-handed. We observed positive associations of non-right-handedness with thought problems, social problems, and being withdrawn and depressed. Externalising problems showed no associations with handedness. Within the thought problems subscale, the effect sizes associated with non-right-handedness for psychotic and non-psychotic items were 0.18 (p=.005) and 0.04 (p=.459), respectively. In conclusion, non-right-handedness is predominantly associated with psychosis-related mental problems as early as in adolescence. Handedness could be taken into account when identifying adolescents at risk for psychosis.

Parkinson-Related Changes of Activation in Visuomotor Brain Regions during Perceived Forward Self-Motion

Radial expanding optic flow is a visual consequence of forward locomotion. Presented on screen, it generates illusionary forward self-motion, pointing at a close vision-gait interrelation. As particularly parkinsonian gait is vulnerable to external stimuli, effects of optic flow on motor-related cerebral circuitry were explored with functional magnetic resonance imaging in healthy controls (HC) and patients with Parkinson’s disease (PD). Fifteen HC and 22 PD patients, of which 7 experienced freezing of gait (FOG), watched wide-field flow, interruptions by narrowing or deceleration and equivalent control conditions with static dots. Statistical parametric mapping revealed that wide-field flow interruption evoked activation of the (pre-)supplementary motor area (SMA) in HC, which was decreased in PD. During wide-field flow, dorsal occipito-parietal activations were reduced in PD relative to HC, with stronger functional connectivity between right visual motion area V5, pre-SMA and cerebellum (in PD without FOG). Non-specific ‘changes’ in stimulus patterns activated dorsolateral fronto-parietal regions and the fusiform gyrus. This attention-associated network was stronger activated in HC than in PD. PD patients thus appeared compromised in recruiting medial frontal regions facilitating internally generated virtual locomotion when visual motion support falls away. Reduced dorsal visual and parietal activations during wide-field optic flow in PD were explained by impaired feedforward visual and visuomotor processing within a magnocellular (visual motion) functional chain. Compensation of impaired feedforward processing by distant fronto-cerebellar circuitry in PD is consistent with motor responses to visual motion stimuli being either too strong or too weak. The ‘change’-related activations pointed at covert (stimulus-driven) attention.

Multiparametric MR Imaging of Diffusion and Perfusion in Contrast-enhancing and Nonenhancing Components in Patients with Glioblastoma

Purpose To determine whether regions of low apparent diffusion coefficient (ADC) with high relative cerebral blood volume (rCBV) represented elevated choline (Cho)-to-N-acetylaspartate (NAA) ratio (hereafter, Cho/NAA ratio) and whether their volumes correlated with progression-free survival (PFS) and overall survival (OS) in patients with glioblastoma (GBM). Materials and Methods This retrospective analysis was approved by the local research ethics committee. Volumetric analysis of imaging data from 43 patients with histologically confirmed GBM was performed. Patients underwent preoperative 3-T magnetic resonance imaging with conventional, diffusion-weighted, perfusion-weighted, and spectroscopic sequences. Patients underwent subsequent surgery with adjuvant chemotherapy and radiation therapy. Overlapping low-ADC and high-rCBV regions of interest (ROIs) (hereafter, ADC-rCBV ROIs) were generated in contrast-enhancing and nonenhancing regions. Cho/NAA ratio in ADC-rCBV ROIs was compared with that in control regions by using analysis of variance. All resulting ROI volumes were correlated with patient survival by using multivariate Cox regression. Results ADC-rCBV ROIs within contrast-enhancing and nonenhancing regions showed elevated Cho/NAA ratios, which were significantly higher than those in other abnormal tumor regions (P < .001 and P = .008 for contrast-enhancing and nonenhancing regions, respectively) and in normal-appearing white matter (P < .001 for both contrast-enhancing and nonenhancing regions). After Cox regression analysis controlling for age, tumor size, resection extent, O-6-methylguanine-DNA methyltransferase-methylation, and isocitrate dehydrogenase mutation status, the proportional volume of ADC-rCBV ROIs in nonenhancing regions significantly contributed to multivariate models of OS (hazard ratio, 1.132; P = .026) and PFS (hazard ratio, 1.454; P = .017). Conclusion Volumetric analysis of ADC-rCBV ROIs in nonenhancing regions of GBM can be used to identify patients with poor survival trends after accounting for known confounders of GBM patient outcome.

Narrowing wide-field optic flow affects treadmill gait in left-sided Parkinson's disease

Radially expanding optic flow is a visual consequence of forward locomotion and supports walking, also in patients with Parkinson’s disease (PD). When presented on a display, it evokes the illusion of forward self-motion. This implies that manipulation of optic flow while walking on a treadmill enables testing the effect of this basic stimulus pattern on gait progression, independent of actual walking. As movements in PD patients are more vulnerable to external stimuli, which may lead to, for example, freezing of gait (FOG), we expected a stronger effect of manipulating optic flow in these patients than in the healthy controls (HC). Fifteen PD patients (8 right-sided symptom dominance [PD.R], 7 left-sided [PD.L]) and 10 matched HCs (mean age, 66.3 years; SD, 7.8) were tested. Patients (mean age, 64.9 years; SD, 7.7 years) were mildly affected (Hoehn & Yahr, 2.3; UPDRS III, 24.3 SD, 7.6) and did not suffer from FOG. At steady-speed walking on the treadmill, narrowing the optic flow field was expected to evoke slowing of gait with backward displacement, mimicking the effect of approaching a narrow corridor. The latter was quantified by center-of-mass calculation. Optic flow is represented by white dots in the lower half of a black screen (171 128 cm). A gradual 1.8-second transition from a wide to a narrow flow field occurred by expanding dark gray surfaces from the horizon in both upward and downward directions (condition Fw-to-Ftn), which provided the natural illusion of moving into the changing environment. Control conditions for nonspecific visual effects were the abrupt transition from wide flow to stationary dots (Fw-to-Sw) and the gradual transition from a wide to a narrow stationary field (Sw-toStn). Given right-hemisphere dominance in visuospatial processing, stronger effects were expected in PD.L. The WAIS block design test was used as a general indicator of right hemisphere function. The transition of narrowing the wide-optic flow field evoked clear gait obstruction, particularly in PD.L (Fig. 1). This suggested a relation with right hemisphere dysfunction, which was supported by the correlation between stronger gait obstruction and lower scores on the WAIS block design in the entire PD group (P1-tailed 1⁄4 .016, r 1⁄4 0.552). Although patient numbers were rather small after splitting into PD.L and PD.R groups, the novel paradigm of manipulating optic flow during treadmill gait appears to provide a promising strategy to study the effects of basic visual stimulus features on gait control. The effect particularly in PD.L is consistent with right-hemisphere dominance concerning visuomotor transformations, also in gait. Enhanced stimulus effects on movements in PD may be a consequence of reduced output from basal ganglia–thalamic circuitry to the lateral premotor cortex, leaving an overruling effect of parietally transferred visual information. As the output of basal ganglia–thalamic circuitry to medial frontal regions may be FIG. 1. Effect of narrowing optic flow on treadmill position and correlation with block design test. A: Mean backward displacement on the treadmill (with standard error) is expressed by positive values (in centimeters), comparing the mean position in the 1.8-second frame after and 1.8 seconds before transition onset in the visual display (P < .05). B: Right hemisphere involvement in backward displacement of Parkinson’s disease patients during the treadmill gait is expressed by the correlation between the block design test and the effect of the transition from a wide to narrow forward optic flow field (Fw-to-Ftn). The thick line shows the overall regression, R 5 0.305. The separate regression lines for PD.L and PD.R patients are constituted by thin dashes and dots, respectively. Abbreviations: PD.L, Parkinson’s disease with left-sided symptom dominance; PD.R, PD with right-sided symptom dominance; HC, healthy controls; Fw-to-Ftn, transition from wide-flow field to narrow flow; Fw-to-Sw, control transition of wide flow to stationary wide field; Sw-to-Stn, control transition of stationary wide field to stationary narrow field; cm, centimeters.

Relation of 18-F-Dopa PET with hypokinesia-rigidity, tremor and freezing in Parkinson's disease.

Introduction In this retrospective study concerning patients with Parkinsons disease (PD) scanned with 18-F-Dopa PET (N = 129), we looked for an association between reduced 18-F-Dopa uptake and the key PD symptoms tremor and hypokinesia-rigidity. We hypothesized to find a stronger correlation between dopaminergic depletion in the striatum and hypokinesia-rigidity compared to tremor. Methods The onset side of symptoms (documented for 102 patients) as well as the first registered UPDRS (available for 79 patients) was used to correlate with F-Dopa uptake values in the caudate nucleus and putamen in this large retrospective sample. Results Reduced F-Dopa uptake was contralateral to hypokinesia-rigidity symptoms and correlated with its severity (quantified by UPDRS). For tremor severity, no correlation was seen with F-Dopa reduction. Furthermore, freezing of gait correlated with reduced F-Dopa uptake in the putamen of the right hemisphere. Conclusion and discussion Our results, obtained in a large patient group, provides support for the concept that tremor in PD is not only based on a dopamine related pathway but may rely on a different pathway.

Cerebral Activations Related to Writing and Drawing with Each Hand

Background Writing is a sequential motor action based on sensorimotor integration in visuospatial and linguistic functional domains. To test the hypothesis of lateralized circuitry concerning spatial and language components involved in such action, we employed an fMRI paradigm including writing and drawing with each hand. In this way, writing-related contributions of dorsal and ventral premotor regions in each hemisphere were assessed, together with effects in wider distributed circuitry. Given a right-hemisphere dominance for spatial action, right dorsal premotor cortex dominance was expected in left-hand writing while dominance of the left ventral premotor cortex was expected during right-hand writing. Methods Sixteen healthy right-handed subjects were scanned during audition-guided writing of short sentences and simple figure drawing without visual feedback. Tapping with a pencil served as a basic control task for the two higher-order motor conditions. Activation differences were assessed with Statistical Parametric Mapping (SPM). Results Writing and drawing showed parietal-premotor and posterior inferior temporal activations in both hemispheres when compared to tapping. Drawing activations were rather symmetrical for each hand. Activations in left- and right-hand writing were left-hemisphere dominant, while right dorsal premotor activation only occurred in left-hand writing, supporting a spatial motor contribution of particularly the right hemisphere. Writing contrasted to drawing revealed left-sided activations in the dorsal and ventral premotor cortex, Broca’s area, pre-Supplementary Motor Area and posterior middle and inferior temporal gyri, without parietal activation. Discussion The audition-driven postero-inferior temporal activations indicated retrieval of virtual visual form characteristics in writing and drawing, with additional activation concerning word form in the left hemisphere. Similar parietal processing in writing and drawing pointed at a common mechanism by which such visually formatted information is used for subsequent sensorimotor integration along a dorsal visuomotor pathway. In this, the left posterior middle temporal gyrus subserves phonological-orthographical conversion, dissociating dorsal parietal-premotor circuitry from perisylvian circuitry including Brocas area.

Transcallosal connection patterns of opposite dorsal premotor regions support a lateralized specialization for action and perception

Lateralization of higher brain functions requires that a dominant hemisphere collects relevant information from both sides. The right dorsal premotor cortex (PMd), particularly implicated in visuomotor transformations, was hypothesized to be optimally located to converge visuospatial information from both hemispheres for goal‐directed movement. This was assessed by probabilistic tractography and a novel analysis enabling group comparisons of whole‐brain connectivity distributions of the left and right PMd in standard space (16 human subjects). The resulting dominance of contralateral PMd connections was characterized by right PMd connections with left visual and parietal areas, indeed supporting a dominant role in visuomotor transformations, while the left PMd showed dominant contralateral connections with the frontal lobe. Ipsilateral right PMd connections were also stronger with posterior parietal regions, relative to the left PMd connections, while ipsilateral connections of the left PMd were stronger with, particularly, the anterior cingulate, the ventral premotor and anterior parietal cortex. The pattern of dominant right PMd connections thus points to a specific role in guiding perceptual information into the motor system, while the left PMd connections are consistent with action dominance based on a lead in motor intention and fine precision skills.

Diagnostic accuracy of magnetic resonance imaging techniques for treatment response evaluation in patients with head and neck tumors, a systematic review and meta-analysis

Background Novel advanced MRI techniques are investigated in patients treated for head and neck tumors as conventional anatomical MRI is unreliable to differentiate tumor from treatment related imaging changes. Purpose As the diagnostic accuracy of MRI techniques to detect tumor residual or recurrence during or after treatment is variable reported in the literature, we performed a systematic meta-analysis. Data sources Pubmed, EMBASE and Web of Science were searched from their first record to September 23th 2014. Study selection Studies reporting diagnostic accuracy of anatomical, ADC, perfusion or spectroscopy to identify tumor response confirmed by histology or follow-up in treated patients for head and neck tumors were selected by two authors independently. Data analysis Two authors independently performed data extraction including true positives, false positives, true negatives, false negatives and general study characteristics. Meta-analysis was performed using bivariate random effect models when ≥5 studies per test were included. Data synthesis We identified 16 relevant studies with anatomical MRI and ADC. No perfusion or spectroscopy studies were identified. Pooled analysis of anatomical MRI of the primary site (11 studies, N = 854) displayed a sensitivity of 84% (95%CI 72–92) and specificity of 82% (71–89). ADC of the primary site (6 studies, N = 287) showed a pooled sensitivity of 89% (74–96) and specificity of 86% (69–94). Limitations Main limitation are the low, but comparable quality of the included studies and the variability between the studies. Conclusions The higher diagnostic accuracy of ADC values over anatomical MRI for the primary tumor location emphases the relevance to include DWI with ADC for response evaluation of treated head and neck tumor patients.