Extinction – an underdiagnosed phenomenon Rev PR Case Report Patrick Urwin Neurology ST3

48 yr old R handed Reverend Visiting Nottingham Found unresponsive in bath 24/03/12 Left hemiparesis Left hemisensory deficit No PMHx / DHx Rare EtOH / Non-smoker FHx mother DVT post partum

Clinical Course CT brain CT angio distal right ICA occlusion Thrombolysed

CT Brain 24hr post thrombolysis

MRI Brain on Day 5 post infarct DWI ADC

Repatriation Kingston Wd K&C 17/04/12 for rehabilitation Femoral DVT 24/04/12 Enoxaparin Warfarin commenced after 4/52 Vasculitis and thrombophilia screen negative Homonomous hemianopia and left neglect reported in notes Citalopram for post-stroke depression Transferred to NeuroRehab 15/06/12 Normal visual fields on formal testing

Behavioural Assessment of Neglect, Azouvi Forgets to groom or shave the left part of his/her face 1 Experiences difficulty in adjusting his/her left sleeve or slipper 3 Forgets to eat food on the left side of his/her plate Forgets to clean the left side of his/her mouth after eating Experiences difficulty in looking towards the left Forgets about a left part of his/her body (e.g. forgets to put his/her upper limb on the armrest or his/her foot on the wheelchair rest, or forgets to use his/her left arm when he/she needs to) Has difficulty in paying attention to noise ore people addressing him/her from the left Collides with people or objects on the left side, such as doors or furniture (either while walking or driving a wheelchair) Experiences difficulty in finding his/her way towards the left when travelling in familiar places or in the rehabilitation unit n/a Experiences difficulty finding his/her personal belongings in the room or bathroom when they are on the left side 2 18/30 Key: 0 = no neglect; 1= mild neglect; 2 = moderate neglect; 3 = severe neglect

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Extinction testing Computerised test Attention paid to centre of screen Series of numbers displayed centrally * flash up in peripheries up to two quadrants 100ms Pt reports when * seen and where Errors/omission noted All omissions by PR on left when concurrent R stimulus

Search testing Alternative task Inverted T present in 50% Pt reports present or absent Observer records present on L, R or absent and calculates accuracy

GVS Trial PR given GVS by Dr. Wilkinson's team Baseline measures Aug 2012 Repeat at 1/52 following sham GVS 2 further assessments after 5/7 GVS and 2/52 after

Increasing evidence of GVS benefit in neglect E.g. Utz et al. Neuropsychologia. 2011 Apr;49(5):1219-25: “In neglect patients [...] GVS significantly reduced the rightward line bisection error as compared to baseline (without GVS) and sham stimulation”

Unfortunately minimal benefit in PR's extinction No improvement on computerised stimulus testing with * Transient improvement in search task at end of GVS Back to pre-GVS baseline after 1/52 No residual improvement in extinction when pt discharged to intermediate care Sept 2012

Neglect Graded defect Cf field loss (1° visual cortex) Gradually declining awareness or performance moving towards contralesional side Depends on head and thorax position Cf field loss (1° visual cortex) Clear borders, dependent on retinal position Parietal spatial mapping But loss of location in space causes loss of awareness of existence of items Loss of other modalities of sensory information does not cause neglect Is parietal function in attention to identify single next visual target?

Extinction No neglect when single stimulus offered Requires multiple stimuli Ipsilesional stimulation results in neglect of contralesional side Relative relation between stimuli, even if both contralesional Extinction less pronounced for stimuli with parallel pathways Contralesional faces – fusiform gyrus Contralesional spiders – limbic / amydala Extinction in healthy subjects

Extinction vs Neglect ?Spectrum ?Different anatomy Right inferior parietal lobe, affecting both dorsal and ventral visual processing pathways; implicated in both processes No consensus in literature for anatomical explanation

Extinction vs Neglect Why make the diagnosis? Do we miss many? Poorer prognosis in stroke pts with neglect Tailored MDT rehab improves outcome in some patients with neglect Potentially greater benefit with extinction therapy Do we miss many? up to 75% of pts with hemiparesis have neglect or extinction Extinction can still have profound impact Shopping Driving Crossing road

Kerkhoff et al. demonstrated a sustained improvement in tactile extinction in 2 patient with chronic deficits following GVS Unfortunately, we have not demonstrated the same improvement with visual extinction in PR Could there be a role of GVS in diagnosis of visual extinction?

Thanks to Dr David Wilkinson, Senior Lecturer in Psychology & Olga Zubko, Research Associate

References Driver J,Vuilleumier P. Perceptual awareness and its loss in unilateral neglect and extinction. Cognition. 2001; 79: 39-88. Kerkhoffa G, Hildebrandtb H, Reinharta S, Kardinala M, Dimovaa V, Utz KS. A long-lasting improvement of tactile extinction after galvanic vestibular stimulation: Two Sham-stimulation controlled case studies. Neuropsychologia. 2011 Jan; 49(2): 186–195 Utz KS, Keller I, Kardinal M, Kerkhoff G. Galvanic vestibular stimulation reduces the pathological rightward line bisection error in neglect-a sham stimulation-controlled study. Neuropsychologia. 2011 Apr; 49(5): 1219- 25. Vossel S, Eschenbeck P, Weiss PH, Weidner R, Saliger J, Karbe H, Fink GR. Visual extinction in relation to visuospatial neglect after right- hemispheric stroke: quantitative assessment and statistical lesion- symptom mapping. J Neurol Neurosurg Psychiatry. 2011; 82: 862-868. Wilkinson D, Zubko O, Degutis J, Milberg W, Potter J. Improvement of a figure copying deficit during subsensory galvanic vestibular stimulation. J Neuropsychol. 2010 Mar; 4(1):107-18.