Monika Fruhmann Berger

Subjective visual vertical (SVV) determined in a representative sample of 15 patients with pusher syndrome

Sirs: A recent study of Saj and colleagues [16] investigated the perception of the subjective visual vertical (SVV) in a small group of 4 subacute stroke patients with pusher syndrome following the development of a right hemisphere lesion. Hemiparetic stroke patients with ‘‘pusher syndrome’’ show the peculiar behavior of using the nonaffected arm or leg to actively push away from the unparalyzed side [7, 11]. The disorder is associated with a severe misperception of the patient’s own upright body orientation, indicated by a marked lateral tilt of the subjective postural vertical (SPV) of nearly 20 [12]. Adjustment of the SPV reflects the perceived upright orientation of the body. Blindfolded subjects are seated on a lateral tilt chair that is passively tilted by the experimenter while subjects are immobilised by lateral stabilisation and indicate verbally or by button press when the chair brings their body in an ‘upright’ position [6, 15, 18]. The marked lateral SPV tilt in pusher patients indicates that these subjects are no longer able to determine when their body is oriented in an erect position. They misperceive their body as oriented ‘upright’ when actually tilted by nearly 20 to the side [12]. Other than SPV perception, the subjective visual vertical (SVV) provides a sensitive and direction-specific measurement of peripheral and central vestibular dysfunction [4]. Saj and colleagues [16] measured the SVV in their 4 pusher patients under either an upright sitting or supine lying posture with the test device placed in front of the subject or in the left or right hemispace. When the subject was sitting and the device positioned in the center, the 4 pusher patients showed an average tilt of the SVV of + 4.8 . Under very similar experimental conditions, a previous study had measured the SVV in 5 patients with pusher syndrome following a right hemisphere lesion [12]. These authors observed an average SVV tilt of )0.4 . Both studies by Karnath et al. [12] and by Saj et al. [16] used small sample sizes of n = 5 and n = 4 pusher patients respectively. This might explain the apparent discrepancy between the SVV measures obtained in the two experiments. The present study thus re-investigated the perception of SVV in a more representative sample consisting of 15 stroke patients with severe pusher syndrome. These patients were consecutively admitted to our department from 2003 on. In addition, 10 non brain-damaged control subjects were examined (age: median 66.5, range 41–84) in the same time period. Stroke patients were included if they demonstrated an acute unilateral, cortical and/or subcortical brain lesion by magnetic resonance imaging (MRI) or by computed tomography (SpiralCT). Contraversive pushing was assessed by using the standardized ‘Scale for Contraversive Pushing’ (SCP) [11, 12]. All subjects or their relatives gave their informed consent to participate in the study, which was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. Demographic and clinical data of all 15 pusher patients are presented in Table 1. The SVV was measured as soon as the patients were able to leave the ward in a wheelchair to be tested in a completely darkened room (cf. Tab. 1). It was determined using a 7.5 cm long luminous rod presented in front of the upright sitting subject at eye level. The luminous rod was attached to a dial which could be rotated within a range of ± 90 from the true vertical orientation. The orientation of the rod was determined by a potentiometer which registered the orientation with an accuracy of 0.1 . From a random angular offset of at least 35 either to the left or the right, the subject was asked to set the rod to earthvertical. To exclude any biases induced by motor or visuo-motor co-ordination deficits following a brain lesion, adjustments of rod orientation were made by the experimenter in a stop-and-go procedure following the verbal instructions of the patients and their controls. Ten SVV adjustments were conducted, 5 with an initial left-sided and 5 with an initial right-sided offset, in alterLETTER TO THE EDITORS J Neurol (2006) 253 : 1367–1369 DOI 10.1007/s00415-006-0216-x

Time- and frequency-domain parameters of heart rate variability and sympathetic skin response in Parkinson's disease

The autonomic nervous system (ANS) is regularly affected in Parkinson’s disease (PD). Information on autonomic dysfunction can be derived from e.g. altered heart rate variability (HRV) and sympathetic skin response (SSR). Such parameters can be quantified easily and measured repeatedly which might be helpful for evaluating disease progression and therapeutic outcome. In this 2-center study, HRV and SSR of 45 PD patients and 26 controls were recorded. HRV was measured during supine metronomic breathing and analyzed in time- and frequency-domains. SSR was evoked by repetitive auditory stimulation. Various ANS parameters were compared (1) between patients and healthy controls, (2) to clinical scales (Unified Parkinson’s disease rating scale, Mini-Mental State Examination, Becks Depression Inventory), and (3) to disease duration. Root mean square of successive differences (RMSSD) and low frequency/high frequency (LF/HF) ratio differed significantly between PD and controls. Both, HRV and SSR parameters showed low or no association with clinical scores. Time-domain parameters tended to be affected already at early PD stages but did not consistently change with longer disease duration. In contrast, frequency-domain parameters were not altered in early PD phases but tended to be lower (LF, LF/HF ratio), respectively higher (HF) with increasing disease duration. This report confirms previous results of altered ANS parameters in PD. In addition, it suggests that (1) these ANS parameters are not relevantly associated with motor, behavioral, and cognitive changes in PD, (2) time-domain parameters are useful for the assessment of early PD, and (3) frequency-domain parameters are more closely associated with disease duration.

Evaluation of Progression Markers in the Premotor Phase of Parkinson's Disease: The Progression Markers in the Premotor Phase Study

Background: The clinical diagnosis of Parkinsons disease (PD) is proposed to be too late for the application of beneficial neuroprotective treatment. Thus, it is important to identify and follow individuals at risk for PD in order to gain knowledge about the prodromal course of the disease. Substantia nigra hyperechogenicity (SN+) has been confirmed as a risk factor for PD and appears promising as a predictor of PD, particularly in combination with other putative PD markers. We present the design and initial data of a 2-year longitudinal investigation of subjects proposed to be at high risk of developing PD (HRPD), compared to early PD patients and control subjects. The aim of the presented study is to monitor progression of the neurodegenerative process to motor PD. Methods: In total, 40 HRPD, 16 PD and 41 control individuals were recruited. The HRPD subjects had SN+ and additionally either 1 cardinal PD motor sign or 2 further risk (e.g. positive family history) or prodromal markers (e.g. hyposmia). In this cohort, motor function, olfaction, mood and blood markers will be evaluated every 6 months, complemented by a comprehensive clinical, imaging and electrophysiological assessment. Results: PD, HRPD and control subjects did not differ significantly regarding age, but the HRPD group consisted mainly of males (72.5% of HRPD subjects vs. 43.9% of controls; p = 0.013). Mean disease duration in PD patients was 31 months (range 15-56). HRPD subjects were predominantly recruited according to the occurrence of slight motor signs (HRPD 77.5%, PD 100%, p = 0.05; controls 0%, HRPD vs. controls, p < 0.017). The Unified Parkinsons Disease Rating Scale motor score (mean, range) indicated that the HRPD group (4, 0-12) had values between those of controls (0, 0-2; p < 0.017) and PD subjects (26, 9-55; p < 0.017). Among nonmotor symptoms, hyposmia was more common in both HRPD (47.5%) and PD subjects (75%) than in controls (5.1%; p < 0.017 for both comparisons). Conclusions: Here, we describe the recruitment of a highly enriched-risk cohort and a promising study design to assess progression to motor PD. Whether the HRPD group indeed suffers from early, PD-specific neurodegeneration remains to be verified in the ongoing follow-up examinations.

Time course of eye and head deviation in spatial neglect.

Spatial neglect is characterized by a deviation of the eyes and the head during active search, as well as at rest. Here the authors investigate the hitherto unknown relationship between these striking behaviors in the course of recovery. Gaze, eye-in-head, and head-on-trunk positions were recorded separately under two experimental conditions: (i) at rest (i.e., without any specific requirements, doing nothing) and (ii) during active exploratory search in a large visual array of 240 degrees x 80 degrees over a 10-month period. The authors observed a parallel decrease of eye and head (= gaze) deviation in both conditions, accompanied by a comparable decline in neglect severity. The results strengthen the view that the marked gaze deviation toward the ipsilesional side in patients with spatial neglect is due to a very elementary disturbance of human spatial information processing.

Perfusion imaging of the right perisylvian neural network in acute spatial neglect

Recent studies have suggested a tightly connected perisylvian neural network associated with spatial neglect. Here we investigated whether structural damage in one part of the network typically is accompanied with functional damage in other, structurally intact areas of this network. By combining normalized fluid-attenuated inversion-recovery (FLAIR) imaging, diffusion-weighted imaging (DWI), and perfusion-weighted imaging (PWI) we asked whether or not lesions centering on fronto-temporal regions co-occur with abnormal perfusion in structurally intact parietal cortex. With thresholds applied to delineate behaviourally relevant malperfusion of brain tissue, the analysis of normalized time-to-peak (TTP) and maximal signal reduction (MSR) perfusion maps did not reveal significant changes outside the area of structural damage. In particular, we found no abnormal perfusion in the structurally intact inferior parietal lobule (IPL) and/or the temporo-parietal junction (TPJ). The present results obtained in three consecutively admitted neglect patients with fronto-temporal lesions indicate that structural damage in one part of the right perisylvian network associated with spatial neglect does not necessarily require dysfunction by malperfusion in other, structurally intact parts of the network to provoke spatial neglect. The neural tissue in the fronto-temporal cortex appears to have an original role in processes of spatial orienting and exploration.

Cognitive Profiles in Parkinson’s Disease and Their Relation to Dementia: A Data-Driven Approach

Parkinsons disease is characterized by a substantial cognitive heterogeneity, which is apparent in different profiles and levels of severity. To date, a distinct clinical profile for patients with a potential risk of developing dementia still has to be identified. We introduce a data-driven approach to detect different cognitive profiles and stages. Comprehensive neuropsychological data sets from a cohort of 121 Parkinsons disease patients with and without dementia were explored by a factor analysis to characterize different cognitive domains. Based on the factor scores that represent individual performance in each domain, hierarchical cluster analyses determined whether subgroups of Parkinsons disease patients show varying cognitive profiles. A six-factor solution accounting for 65.2% of total variance fitted best to our data and revealed high internal consistencies (Cronbachs alpha coefficients >0.6). The cluster analyses suggested two independent patient clusters with different cognitive profiles. They differed only in severity of cognitive impairment and self-reported limitation of activities of daily living function but not in motor performance, disease duration, or dopaminergic medication. Based on a data-driven approach, divers cognitive profiles were identified, which separated early and more advanced stages of cognitive impairment in Parkinsons disease without dementia. Importantly, these profiles were independent of motor progression.

Clinical Characteristics with an Impact on ADL Functions of PD Patients with Cognitive Impairment Indicative of Dementia

Background Dementia in Parkinson’s disease (PD) is defined as cognitive decline severe enough to affect activities of daily living function (ADL). The aim of our exploratory study was to compare two groups of PD patients. Both groups had cognitive deficits severe enough to justify diagnosis of dementia, but they differed according to caregivers’ rating on ADL dysfunction. Parameters which differed between the two groups were interpreted to affect the caregivers’ perception of ADL dysfunction in PD patients with cognitive impairment indicative of Parkinson’s disease dementia. Methodology/Principal Findings Thirty of 131 Parkinson’s disease patients fulfilled the Movement Disorders Society Task Force – recommended, cognitive Level-I-criteria for dementia. According to standardized caregiver ratings, volunteers were grouped into 18 patients with (ADL-) and 12 without instrumental activities of daily living dysfunction (ADL+). Caregiver activities of daily living function ratings closely correlated with self-estimates of patients and those of physician (p<0.001). ADL- patients performed worse on tests assessing visual-construction (p<0.05) and attention (p=0.03) than ADL+ patients. Moreover, the postural instability and gait disorder subtype was more frequent in ADL- patients (p=0.009). ADL- patients tended to have more communication problems (p=0.05), more anxiety (p=0.05) and showed a tendency to be treated more often with neuroleptics (p=0.049) than ADL+. Conclusions/Significance Results indicate that worse attention, visual-construction abilities, the postural instability and gait disorder subtype, communication problems, medication and presence of anxiety are related to activities of daily living dysfunctions in Parkinson’s disease patients with cognitive decline indicative of dementia. Our data suggests that not only cognitive factors but also non-cognitive factors seem to be linked to the diagnosis of Parkinson’s disease dementia associated with significant impact on instrumental activities of daily living function. Further studies with larger sample sizes are needed to verify our results.

Subcortical neglect is not always a transient phenomenon: evidence from a 1-year follow-up study.

Compared to cortical lesions, spatial neglect following subcortical stroke is most frequently seen as a mild and transient phenomenon. Since this assumption is based on only few observations, we reexamined the prognosis and severity of spatial neglect in patients with circumscribed right-sided basal ganglia or thalamic lesions in the acute and in the chronic phase of the stroke. On average, 1.15 years after stroke, spatial neglect had persisted in about 40% of the patients with subcortical lesions. The severity was reduced to about one third. The results argue against the view that spatial neglect following subcortical lesions typically has a favorable prognosis.

Acknowledgements to Referees

N. Cicorella, Mantova, Italy R. Cifkova, Prague, Czech Republic R. Cohen, Providence, R.I., USA W.J. Culpepper, Baltimore, Md., USA C. Curioni, Petrópolis, Brazil L.M. de Lau, Rotterdam, The Netherlands V. Demarin*, Zagreb, Croatia M. Dennis, Edinburgh, UK J. de Pedro Cuesta, Madrid, Spain D.A. De Silva, Singapore, Singapore R. De Silva, Nugegoda, Sri Lanka E. De Valck, Brussels, Belgium Y. Doi, Wako, Japan P. Durai, Punjab, India M. Endziniene, Kaunas, Lithuania S. Evans, Springfield, Ill., USA F. Fang, Stockholm, Sweden W. Feng, Charleston, S.C., USA R. Fernandez-Ballestero, Madrid, Spain J.M. Ferro, Lisbon, Portugal J.L. Fisher, Columbus, Ohio, USA H. Flocas, Athens, Greece R.L. Folmer, Portland, Oreg., USA G. Franklin, Seattle, Wash., USA L. Fratiglioni, Stockholm, Sweden G.D. Friedman, Oakland, Calif., USA D. Frydecka, Wroclaw, Poland M.J. Futter, Cape Town, South Africa M. Giroud, Dijon, France W. Grisold, Wien, Austria F. Grodstein, Boston, Mass., USA Q.H. Guo, Shanghai, China W.A. Hauser*, New York, N.Y., USA P. Heuschmann, Münster, Germany R. Hilsabeck, Encino, Calif., USA M. Himle, Salt Lake City, Utah, USA B. Hocking, Camberwell, Vic., Australia E. Hogervorst, Loughborough, UK X. Huang, Hershey, Pa., USA G.G. Iuliano, Salerno, Italy J. Jirsch, Montréal, Qué., Canada L. Abdullah, Sarasota, Fla., USA S. Adamovich, Newark, N.J., USA A. Adem, Al Ain, United Arab Emirates H. Akiyuki*, Chiba, Japan T. Ala, Springfield, Ill., USA M. Alashari, Al Ain, United Arab Emirates S.M. Albert, Pittsburg, Pa., USA A. Ali, Kingston, Jamaica A. Alperovitch, Paris, France M. Alter, Wynnewood, Pa., USA L.-C. Alvaro*, Bilbao, Spain A. Anand, Chandigarh, India C. Armon, Springfield, Ill., USA V.V. Ashraf, Calicut, India A. Barber, Auckland, New Zealand S. Barker-Collo, Auckland, New Zealand L. Batistin, Padua, Italy L. Bayentin, Québec, Qué., Canada B. Baykan, Istanbul, Turkey E. Beghi*, Milano, Italy J. Benito-Leon*, Madrid, Spain J. Berciano, Santander, Spain D. Bereczki, Budapest, Hungary D. Berger, Cortland, N.Y., USA F. Bermejo-Pareja, Madrid, Spain N. Bharucha, Mumbai, India R. Biswas, Bhopal, India F. Bonvicini, Reggio Emilia, Italy G. Boysen*, Copenhagen, Denmark M. Brainin, Krems, Austria A.M. Brickman, New York, N.Y., USA R. Brouns, Antwerp, Belgium N. Cabral, Joinville, Brazil S.F. Cappa*, Milano, Italy A. Carolei, L’Aquila, Italy D. Carpenter, Rensselaer, N.Y., USA T.D. Carter, Melbourne, Vic., Australia J.M. Castellote Olivito, Madrid, Spain H. Chen, Research Triangle Park, N.C., USA A. Chio, Torino, Italy

Contents Vol. 41, 2013

223 3rd International Congress on Neurology and Epidemiology Abu Dhabi, UAE, November 21–23, 2013 Editors: Feigin, V.L. (Auckland); Saadah, M. (Abu Dhabi) (available online only) 221 Acknowledgements to Referees