Structural white-matter connections mediating distinct behavioral components of spatial neglect in right brain-damaged patients

60 There is little published evidence for protection of white matter with neuroprotective drugs in animal models of stroke, yet white matter protection may be important in achieving clinical efficacy. We have examined the effects of NXY-059, a nitrone-based free radical trapping agent, on long-term functional disability in a primate model of stroke. We also examined histopathological effects, including analyses of grey and white matter damage. Five minutes after unilateral permanent middle cerebral artery occlusion, marmosets received a 1 ml i.v. infusion of saline (n=5) or NXY-059 (28 mg/kg) (n=6) and osmotic minipumps (model 2001D) were implanted s.c. to provide continuous drug or saline infusion for 48 h. Drug-filled pumps released NXY-059 at a rate of approximately 16 mg/kg/h. The plasma unbound drug concentration at 24 h was 76.3 ± 5.7 μM, a level well tolerated in acute stroke patients. The monkeys had been trained and tested on a variety of behavioral tasks before surgery. NXY-059-treated monkeys were significantly better at reaching with their contralesional arm than were saline-treated monkeys when re-tested 3 (p<0.01) and 10 weeks (p<0.01) after surgery. NXY-059-treatment also significantly reduced spatial neglect measured 3 weeks after surgery (p<0.01) compared with the saline group. After behavioral testing was complete, histopathological analysis showed NXY-059-treated monkeys had significantly smaller infarcts than saline-treated monkeys (F (1, 10)=5.21, p<0.05). NXY-059 reduced overall infarct size by 51%, damage to the cortex was reduced by 54%, white matter by 52%, caudate by 49%, and putamen by 33% compared with saline-treated monkeys. In conclusion, NXY-059 substantially lessened the functional disability in these monkeys. This drug protects not only cortical tissue, but also white matter and subcortical structures against ischemic damage. Together these findings bode well for advancing this drug to further clinical trials for its use in acute stroke.

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Spatial Neglect and Anosognosia After Right Brain Stroke

CONTINUUM Lifelong Learning in Neurology ◽

10.1212/con.0000000000001076 ◽

2021 ◽

Vol 27 (6) ◽

pp. 1624-1645

Author(s):

A. M. Barrett

Keyword(s):

Spatial Neglect ◽

Right Brain ◽

Brain Stroke

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Concomitant recovery from left spatial neglect and inflammatory dysfunction of white-matter pathways in a case of acute disseminated encephalo-myelitis (ADEM)

Cortex ◽

10.1016/j.cortex.2019.04.018 ◽

2019 ◽

Vol 119 ◽

pp. 231-236

Author(s):

Francesco Tomaiuolo ◽

Serena Campana ◽

Luca Cecchetti ◽

Rosita Galli ◽

Gesualdo M. Zucco ◽

...

Keyword(s):

White Matter ◽

Spatial Neglect

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Small numbers in the right brain: Evidence from patients without and with spatial neglect

Cortex ◽

10.1016/j.cortex.2012.06.002 ◽

2013 ◽

Vol 49 (1) ◽

pp. 348-351 ◽

Cited By ~ 21

Author(s):

Marilena Aiello ◽

Sheila Merola ◽

Fabrizio Doricchi

Keyword(s):

Spatial Neglect ◽

Right Brain ◽

The Right

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Damage to White Matter Pathways in Subacute and Chronic Spatial Neglect: A Group Study and 2 Single-Case Studies with Complete Virtual "In Vivo" Tractography Dissection

Cerebral Cortex ◽

10.1093/cercor/bhs351 ◽

2012 ◽

Vol 24 (3) ◽

pp. 691-706 ◽

Cited By ~ 175

Author(s):

M. Thiebaut de Schotten ◽

F. Tomaiuolo ◽

M. Aiello ◽

S. Merola ◽

M. Silvetti ◽

...

Keyword(s):

White Matter ◽

Case Studies ◽

Single Case ◽

Spatial Neglect

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Measuring Gaze and Arrow Cuing Effects With a Short Test Adapted to Brain Damaged Patients With Unilateral Spatial Neglect: A Preliminary Study

Frontiers in Psychology ◽

10.3389/fpsyg.2021.690197 ◽

2021 ◽

Vol 12 ◽

Author(s):

Rindra Narison ◽

Marie de Montalembert ◽

Andrew Bayliss ◽

Laurence Conty

Keyword(s):

Older Patients ◽

Brain Lesion ◽

Brain Lesions ◽

Spatial Neglect ◽

Short Version ◽

Unilateral Spatial Neglect ◽

Right Brain ◽

Short Test ◽

Preliminary Study ◽

Healthy Participants

People with left unilateral spatial neglect (USN) following a right brain lesion show difficulty in orienting their attention toward stimuli presented on the left. However, cuing the stimuli with gaze direction or a pointing arrow can help some of them to compensate for this difficulty. In order to build a tool that helps to identify these patients, we needed a short version of the paradigm classically used to test gaze and arow cuing effects in healthy adults, adapted to the capacities of patients with severe attention deficit. Here, we tested the robustness of the cuing effects measured by such a short version in 48 young adult healthy participants, 46 older healthy participants, 10 patients with left USN following a right brain lesion (USN+), and 10 patients with right brain lesions but no USN (USN–). We observed gaze and arrow cuing effects in all populations, independently of age and presence or absence of a right brain lesion. In the neglect field, the USN+ group showed event greater cuing effect than older healthy participants and the USN– group. We showed that gaze and arrow cuing effects are powerful enough to be detected in a very short test adapted to the capacities of older patients with severe attention deficits, which increases their applicability in rehabilitation settings. We further concluded that our test is a suitable basis to develop a tool that will help neuropsychologists to identify USN patients who respond to gaze and/or arrow cuing in their neglect field.

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Disconnections in Personal Neglect

10.21203/rs.3.rs-1126909/v1 ◽

2021 ◽

Author(s):

Sara Bertagnoli ◽

Valentina Pacella ◽

Elena Rossato ◽

Paul M Jenkinson ◽

Akaterini Fotopoulou ◽

...

Keyword(s):

White Matter ◽

Right Hemisphere ◽

Temporal Cortex ◽

Lesion Size ◽

The Body ◽

Spatial Neglect ◽

Small Samples ◽

Motor Deficits ◽

The Novel ◽

Extrapersonal Space

Abstract Personal neglect is a disorder in the perception and representation of the body that causes the patients to behave as if the contralesional side of their body does not exist. This clinical condition has not been adequately investigated in the past as it has been considered a symptom of unilateral spatial neglect, which has mainly been studied with reference to extrapersonal space. Only a few studies with small samples have investigated the neuroanatomical correlates of personal neglect, and these have mainly focused on discrete cortical lesions and modular accounts, as well as being based on the hypothesis that this disorder is associated with somatosensory and spatial deficits. In the present study, we tested the novel hypothesis that personal neglect may be associated not only with discrete cortical and subcortical lesions, but also with disconnections of white matter tracts. We performed an advanced lesion analyses in a large sample of 104 right hemisphere damaged patients, 68 of whom were suffering from personal neglect. Results from the analyses of the grey and white matter were controlled for co-occurrent clinical variables such as extrapersonal neglect, anosognosia for hemiplegia and motor deficits, along with other lesion-related variables such as lesion size, the interval from the lesion onset to neuroimaging recordings. Our results reveal that personal neglect is associated with lesions in a medial network which involves the temporal cortex (Heschl’s gyrus), the ventro-lateral nuclei of the thalamus, and the fornix. This suggests that personal neglect involves a convergence between sensorimotor processes, spatial representation and the processing of self-referred information (episodic memory).

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