Spontaneous visual exploration during locomotion in patients with phobic postural vertigo.

BACKGROUND: Earlier studies on stance and gait with posturographic and EMG-recordings and automatic gait analysis in patients with phobic postural vertigo (PPV) or visual height intolerance (vHI) revealed similar patterns of body stiffening with muscle co-contraction and a slow, cautious gait. Visual exploration in vHI patients was characterized by a freezing of gaze-in-space when standing and reduced horizontal eye and head movements during locomotion. OBJECTIVE: Based on the findings in vHI patients, the current study was performed with a focus on visual control of locomotion in patients with PPV while walking along a crowded hospital hallway. METHODS: Twelve patients with PPV and eleven controls were recruited. Participants wore a mobile infrared video eye-tracking system that continuously measured eye-in-head movements in the horizontal and vertical planes and head orientation and motion in the yaw, pitch, and roll planes. Visual exploration behavior of participants was recorded at the individually preferred speed for a total walking distance of 200 m. Gaze-in-space directions were determined by combining eye-in-head and head-in-space orientation. Walking speeds were calculated based on the trial duration and the total distance traversed. Participants were asked to rate their feelings of discomfort during the walk on a 4-point numeric rating scale. The examiners rated the crowdedness of the hospital hallway on a 4-point numeric rating scale. RESULTS: The major results of visual exploration behavior in patients with PPV in comparison to healthy controls were: eye and head positions were directed more downward in the vertical plane towards the ground ahead with increased frequency of large amplitude vertical orientation movements towards the destination, the end of the ground straight ahead. The self-adjusted speed of locomotion was significantly lower in PPV. Particularly those patients that reported high levels of discomfort exhibited a specific visual exploration of their horizontal surroundings. The durations of fixating targets in the visual surroundings were significantly shorter as compared to controls. CONCLUSION: Gaze control of locomotion in patients with PPV is characterized by a preferred deviation of gaze more downward and by horizontal explorations for suitable auxiliary means for potential postural support in order to prevent impending falls. These eye movements have shorter durations of fixation as compared to healthy controls and patients with vHI. Finally, the pathological alterations in eye-head coordination during locomotion correlate with a higher level of discomfort and anxiety about falling.

Approach to an experimental model of Mal de Debarquement Syndrome.

INTRODUCTION: Mal de Debarquement Syndrome (MdDS) is the rare condition of enduring rocking sensations and subjective unsteadiness following a lengthy exposure to passive motion. The pathogenesis of MdDS is unknown and the available treatment is limited. Here, we developed an experimental model of MdDS that may facilitate systematic inquiry of MdDS pathophysiology and the development of prevention or treatment strategies for this condition. METHODS: In an initial series of pilot experiments, suitable stimulation devices and conditions were evaluated. The final paradigm consisted of a low-frequency oscillatory motion stimulation, simultaneously deployed as roll and pitch rotation as well as heave on a six-degrees-of-freedom motion platform. Twelve healthy participants were stimulated under this condition for 30 min during free stance. Aftereffects with respect to rocking sensations and posturographic sway were monitored up to 60 min post-stimulation and compared to an initial pre-stimulation assessment as well as to posturographic recordings of spontaneous sway in ten patients with MdDS. RESULTS: Motion stimulation consistently evoked MdDS-like rocking sensations and postural alterations that lasted up to 45 min after cessation of passive motion exposure. Body sway alterations were most pronounced in anterior-posterior dimension during standing with eyes closed and primarily characterized by a distinct peak in the low-frequency sway spectrum close to stimulation frequency. These postural aftereffects further closely resembled spontaneous oscillatory low-frequency sway observed in patients with MdDS. CONCLUSION: Subsequent neurophysiological and imaging examinations are required to investigate whether the model of transient, experimental MdDS actually shares a common substrate with the enduring pathological condition of MdDS.

The novel MKL target gene myoferlin modulates expansion and senescence of hepatocellular carcinoma.

Megakaryoblastic Leukemia 1 and 2 (MKL1/2) are transcriptional coactivators of Serum Response Factor (SRF) with an essential role for hepatocellular carcinoma (HCC) growth and oncogene-induced senescence. In this report, we identified myoferlin as a novel MKL/SRF target gene by gene expression profiling and verification in vivo in HCC xenografts. Myoferlin was overexpressed in human and murine HCCs triggered by conditional expression of constitutively active SRF-VP16 protein in hepatocytes. Furthermore, myoferlin was required for HCC cell invasion, proliferation and anchorage-independent cell growth. We provide evidence that myoferlin is a crucial gene target of MKL1/2 mediating its effect on oncogene-induced senescence by modulating the activation state of the EGFR and downstream MAPK and p16-/Rb pathways. Depletion of myoferlin in tumour cells from SRF-VP16-derived murine HCCs induced a senescence phenotype. These findings identify MKL1/2 and myoferlin as novel therapeutic targets to treat human HCC by a senescence-inducing strategy.