Perfusion Imaging in Pusher Syndrome to Investigate the Neural Substrates Involved in Controlling Upright Body Position

Brain damage may induce a dysfunction of upright body position termed “pusher syndrome”. Patients with such disorder suffer from an alteration of their sense of body verticality. They experience their body as oriented upright when actually tilted nearly 20 degrees to the ipsilesional side. Pusher syndrome typically is associated with posterior thalamic stroke; less frequently with extra-thalamic lesions. This argued for a fundamental role of these structures in our control of upright body posture. Here we investigated whether such patients may show additional functional or metabolic abnormalities outside the areas of brain lesion. We investigated 19 stroke patients with thalamic or with extra-thalamic lesions showing versus not showing misperception of body orientation. We measured fluid-attenuated inversion-recovery (FLAIR) imaging, diffusion-weighted imaging (DWI), and perfusion-weighted imaging (PWI). This allowed us to determine the structural damage as well as to identify the malperfused but structural intact tissue. Pusher patients with thalamic lesions did not show dysfunctional brain areas in addition to the ones found to be structurally damaged. In the pusher patients with extra-thalamic lesions, the thalamus was neither structurally damaged nor malperfused. Rather, these patients showed small regions of abnormal perfusion in the structurally intact inferior frontal gyrus, middle temporal gyrus, inferior parietal lobule, and parietal white matter. The results indicate that these extra-thalamic brain areas contribute to the network controlling upright body posture. The data also suggest that damage of the neural tissue in the posterior thalamus itself rather than additional malperfusion in distant cortical areas is associated with pusher syndrome. Hence, it seems as if the normal functioning of both extra-thalamic as well as posterior thalamic structures is integral to perceiving gravity and controlling upright body orientation in humans.

[1]  L. Gauthier,et al.  The Bells Test: A quantitative and qualitative test for visual neglect. , 1989 .

[2]  Katrin Amunts,et al.  White matter fiber tracts of the human brain: Three-dimensional mapping at microscopic resolution, topography and intersubject variability , 2006, NeuroImage.

[3]  A M Bronstein,et al.  The perception of body verticality (subjective postural vertical) in peripheral and central vestibular disorders. , 1996, Brain : a journal of neurology.

[4]  S. Engelborghs,et al.  Functional anatomy, vascularisation and pathology of the human thalamus. , 1998, Acta neurologica Belgica.

[5]  J W Belliveau,et al.  Functional cerebral imaging by susceptibility‐contrast NMR , 1990, Magnetic resonance in medicine.

[6]  J. Baron,et al.  Effects of thalamic stroke on energy metabolism of the cerebral cortex. A positron tomography study in man. , 1986, Brain : a journal of neurology.

[7]  Chris Rorden,et al.  Improving Lesion-Symptom Mapping , 2007, Journal of Cognitive Neuroscience.

[8]  A Gregory Sorensen,et al.  CT and conventional and diffusion-weighted MR imaging in acute stroke: study in 691 patients at presentation to the emergency department. , 2002, Radiology.

[9]  A Gregory Sorensen,et al.  Predicting cerebral ischemic infarct volume with diffusion and perfusion MR imaging. , 2002, AJNR. American journal of neuroradiology.

[10]  L. Krubitzer,et al.  Thalamocortical connections of anterior and posterior parietal cortical areas in New World titi monkeys , 2006, The Journal of comparative neurology.

[11]  G Mann,et al.  ON THE THALAMUS * , 1905, British medical journal.

[12]  S. Weintraub,et al.  Mental state assessment of young and elderly adults in behavioral neurology , 1985 .

[13]  P. Schlindwein,et al.  Cortical representation of saccular vestibular stimulation: VEMPs in fMRI , 2008, NeuroImage.

[14]  P. Ashby,et al.  Associated postural adjustments are impaired by a lesion of the cortex , 1996, Neurology.

[15]  H. Karnath Pusher Syndrome – a frequent but little-known disturbance of body orientation perception , 2007, Journal of Neurology.

[16]  Leif Johannsen,et al.  How Efficient is a Simple Copying Task to Diagnose Spatial Neglect in its Chronic Phase? , 2004, Journal of clinical and experimental neuropsychology.

[17]  M. Mesulam Principles of behavioral neurology , 1985 .

[18]  K. Uemura,et al.  MRI of acute cerebral infarction: a comparison of FLAIR and T2-weighted fast spin-echo imaging , 1997, Neuroradiology.

[19]  J. Lorberbaum,et al.  A review of functional neuroimaging studies of vagus nerve stimulation (VNS). , 2003, Journal of psychiatric research.

[20]  J. Masdeu,et al.  Posterior thalamic hemorrhage induces “pusher syndrome” , 2005, Neurology.

[21]  E. M. Rouiller,et al.  Thalamocortical and the dual pattern of corticothalamic projections of the posterior parietal cortex in macaque monkeys , 2007, Neuroscience.

[22]  D M Reboussin,et al.  A comparison of fast spin-echo, fluid-attenuated inversion-recovery, and diffusion-weighted MR imaging in the first 10 days after cerebral infarction. , 1999, AJNR. American journal of neuroradiology.

[23]  C. L. Shupert,et al.  Vestibular and somatosensory contributions to responses to head and body displacements in stance , 1994, Experimental Brain Research.

[24]  R. Watts,et al.  Cerebral Activation during Vagus Nerve Stimulation: A Functional MR Study , 2002, Epilepsia.

[25]  T. Brandt,et al.  Thalamic infarctions , 1993, Neurology.

[26]  D G Gadian,et al.  Quantification of Perfusion Using Bolus Tracking Magnetic Resonance Imaging in Stroke: Assumptions, Limitations, and Potential Implications for Clinical Use , 2002, Stroke.

[27]  F Mauguière,et al.  Thalamocortical diaschisis: positron emission tomography in humans. , 1992, Journal of neurology, neurosurgery, and psychiatry.

[28]  Thomas Bauermann,et al.  Evidence for cortical visual substitution of chronic bilateral vestibular failure (an fMRI study). , 2007, Brain : a journal of neurology.

[29]  Roland Bammer,et al.  Influence of Arterial Input Function on Hypoperfusion Volumes Measured With Perfusion-Weighted Imaging , 2003, Stroke.

[30]  H. Karnath,et al.  Spontaneous eye and head position in patients with spatial neglect , 2005, Journal of Neurology.

[31]  Rüdiger Wenzel,et al.  Human Vestibular Cortex as Identified with Caloric Stimulation in Functional Magnetic Resonance Imaging , 2002, NeuroImage.

[32]  R. Cubelli,et al.  Impairments of trunk movements following left or right hemisphere lesions: dissociation between apraxic errors and postural instability. , 2003, Brain : a journal of neurology.

[33]  D. Bohning,et al.  Feasibility of Vagus Nerve Stimulation–Synchronized Blood Oxygenation Level–Dependent Functional MRI , 2001, Investigative radiology.

[34]  Philippe Kahane,et al.  Reappraisal of the human vestibular cortex by cortical electrical stimulation study , 2003, Annals of neurology.

[35]  Leif Østergaard,et al.  Magnetic Resonance Perfusion-Weighted Imaging of Acute Cerebral Infarction: Effect of the Calculation Methods and Underlying Vasculopathy , 2002, Stroke.

[36]  D Atkinson,et al.  Fluid-attenuated inversion recovery (FLAIR) for assessment of cerebral infarction. Initial clinical experience in 50 patients. , 1996, Stroke.

[37]  Chris Rorden,et al.  Spatial Normalization of Brain Images with Focal Lesions Using Cost Function Masking , 2001, NeuroImage.

[38]  Bernard Gibaud,et al.  Detection of Inter-hemispheric Asymmetries of Brain Perfusion in SPECT , 2002, MICCAI.

[39]  H. Karnath,et al.  Using human brain lesions to infer function: a relic from a past era in the fMRI age? , 2004, Nature Reviews Neuroscience.

[40]  H. Ellis stroke , 1997, The Lancet.

[41]  A. C. Santos,et al.  Contraversive pushing in non-stroke patients , 2004, Journal of Neurology.

[42]  Timothy Edward John Behrens,et al.  Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging , 2003, Nature Neuroscience.

[43]  Simon B. Eickhoff,et al.  A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data , 2005, NeuroImage.

[44]  Leif Johannsen,et al.  Normalized perfusion MRI to identify common areas of dysfunction: patients with basal ganglia neglect. , 2005, Brain : a journal of neurology.

[45]  Hans-Otto Karnath,et al.  Understanding and treating "pusher syndrome". , 2003, Physical therapy.

[46]  Timothy Edward John Behrens,et al.  Functional-anatomical validation and individual variation of diffusion tractography-based segmentation of the human thalamus. , 2005, Cerebral cortex.

[47]  T. Brandt,et al.  Thalamic infarctions cause side-specific suppression of vestibular cortex activations. , 2005, Brain : a journal of neurology.

[48]  L. Johannsen,et al.  "Pusher syndrome" following cortical lesions that spare the thalamus , 2006, Journal of Neurology.

[49]  J. Masdeu,et al.  Thalamic astasia: Inability to stand after unilateral thalamic lesions , 1988, Annals of neurology.

[50]  R J Seitz,et al.  Diffusion- and perfusion-weighted MRI. The DWI/PWI mismatch region in acute stroke. , 1999, Stroke.

[51]  J. Dichgans,et al.  The neural representation of postural control in humans. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[52]  H Mittelstaedt,et al.  Origin and processing of postural information , 1998, Neuroscience & Biobehavioral Reviews.

[53]  A. Hillis,et al.  Hypoperfusion of Wernicke's area predicts severity of semantic deficit in acute stroke , 2001, Annals of neurology.

[54]  H Mittelstaedt,et al.  Basic control patterns of orientational homeostasis. , 1964, Symposia of the Society for Experimental Biology.

[55]  Fu-Nien Wang,et al.  A Reinvestigation of Maximal Signal Drop in Dynamic Susceptibility Contrast Magnetic Resonance Imaging , 2002, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[56]  R J Seitz,et al.  Diffusion- and perfusion-weighted MRI: influence of severe carotid artery stenosis on the DWI/PWI mismatch in acute stroke. , 2000, Stroke.

[57]  L. Johannsen,et al.  Subjective visual vertical (SVV) determined in a representative sample of 15 patients with pusher syndrome , 2006, Journal of Neurology.

[58]  J. Massion Postural control system , 1994, Current Opinion in Neurobiology.

[59]  M Dieterich,et al.  Vestibular cortex lesions affect the perception of verticality , 1994, Annals of neurology.

[60]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[61]  J. Dichgans,et al.  The origin of contraversive pushing , 2000, Neurology.