The rehabilitation of hemispatial neglect after stroke

Neurologists Begoña González, Elena Muñoz and Juan Pablo Romero present Transcranial direct current stimulation (tDCS) as a method for the rehabilitation of hemineglect after stroke.

Definition of hemineglect and functional consequences

Hemineglect involves a difficulty attending to the contralateral hemifield (usually the left) of the lesioned brain area, and can range from an omission of objects located in the left hemifield of space to a lack of attention, recognition and even denial of parts of one’s own body. Functionally, hemineglect leads to severe difficulties in the affected person’s independence, both in basic activities of daily living (personal hygiene, dressing, nutrition, etc.) and instrumental activities (managing money, meal preparation, public transportation or independent ambulation).

In addition, the presence of hemineglect has been associated with longer hospital and rehabilitation stays, a higher risk of falls and poorer motor and functional recovery (Chen et al., 2015; Jehkonen et al., 2006; Wilkinson et al., 2012).

Recovery from hemineglect

Regarding the prognosis of hemineglect recovery, studies conducted between 8 and 12 months after a stroke with hemineglect found that the disorder persisted in one third of cases (Colombo et al., 1982; Karnath et al., 2011) or showed little recovery (Kalra et al., 1997; Katz et al., 1999; Luukkainen-Markkula et al., 2014; Paolucci et al., 2001).

Current therapies

Today, the therapeutic approaches available for hemineglect rehabilitation, such as prism adaptation, visuospatial training, mental imagery therapy or optokinetic stimulation, have limited clinical effectiveness and, in some cases, are short-lived (Azouvi et al., 2017; Fasotti & van Kessel, 2013). Due to the persistence of symptoms and the impact on patient independence, it is essential to develop new treatment methods and properly address the underlying brain dysfunctions. In this regard, interventions based on non-invasive brain stimulation techniques constitute a promising therapeutic approach.

Improving hemineglect through neuromodulation

At the Brain Injury Unit of Hospital Beata María Ana in Madrid a study is being conducted focused on improving hemineglect through neuromodulation via transcranial direct current stimulation (tDCS) aimed at improving hemineglect secondary to stroke in order to enhance the benefits that both interventions have independently.

The research, carried out together with the Universitat Oberta de Catalunya and Francisco de Vitoria University, is co-directed by Dr. Juan Pablo Romero, director of the Brain Injury Neurorehabilitation research group, neurologist of the Brain Injury Unit at Hospital Beata María Ana and professor at Francisco de Vitoria University, and Dr. Elena Muñoz Marrón, director of the Cognitive NeuroLab research group, professor at the UOC School of Health Sciences and director of the Master’s Degree in Neuropsychology. Also participating in the project are Dr. Marcos Ríos-Lago, coordinator of the Brain Injury Unit at Hospital Beata María Ana, Begoña González Rodríguez and David de Noreña Martínez, neuropsychologists of the Unit, and the predoctoral researchers from Francisco de Vitoria University, Francisco Sánchez, Yeray González and Aida Arroyo.

Objective

The objective of this project is to validate a neuromodulation protocol aimed at treating hemineglect secondary to ischemic stroke in patients who are in the subacute phase (3 to 12 months since the injury). This technique seeks to improve symptoms by reducing the pathological hyperactivity that develops in the undamaged hemisphere after a stroke located in the right middle cerebral artery, through the application of a multisite tDCS stimulation program.

Neuromodulation techniques

Non-invasive brain stimulation refers to different neurophysiological techniques that allow modulation of brain activity in a safe and non-invasive manner (Bikson et al., 2016). Through these techniques we can both increase and decrease cortical excitability. The most widely used non-invasive brain stimulation techniques today are transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), for which there is sufficient empirical evidence supporting their potential to modulate brain activity in the short and long term (Hummel & Cohen, 2006).

Transcranial direct current stimulation (tDCS)

tDCS allows the modulation of cortical activity through the application of a low-intensity electric current (generally between 1 mA and 2 mA) by placing two or more electrodes on the patient’s scalp. In this way, the electric current flows between the electrodes, from the anode to the cathode, increasing cortical excitability under the anode and decreasing it under the cathode. Furthermore, multisite tDCS, or high-definition tDCS, allows for more precise and localized stimulation of the selected brain area.

Likewise, tDCS has been shown to be an effective technique as a complementary therapeutic approach to more conventional post-stroke rehabilitation treatments (Edwards & Fregni, 2008), showing promising results in the rehabilitation of visuospatial hemineglect (e.g., Bang & Bong, 2015; Ladavas et al., 2015; Yi et al., 2016).

Based on Kinsbourne’s interhemispheric rivalry model (Kinsbourne, 1977) and depending on stimulation parameters, different stimulation approaches can be considered, such as increasing activity in the lesioned hemisphere, inhibiting the pathological hyperactivity of the healthy hemisphere, or a combination of both (Zebhauser et al., 2019).

tDCS rehabilitation project

In this project we apply a tDCS protocol lasting 20 minutes daily for 10 consecutive days (Monday to Friday), at an intensity of 2 mA. Stimulation is applied with the cathode positioned at P3 (following the international 10/20 system for EEG electrode placement), with the return electrodes distributed at C3, CP5, CP1, Pz, PO3, PO7, P7. The goal of this montage is to reduce the pathological hyperactivation of the parietal cortex of the healthy hemisphere (P3), in order to achieve increased activation and attentional participation of the lesioned (right) hemisphere toward the left hemifield, by reducing the hyperactivity of the contralateral healthy hemisphere which relieves the damaged hemisphere from the inhibition exerted by the healthy one.

Interventions based on non-invasive brain stimulation, such as tDCS, constitute a very promising therapeutic approach, with minimal adverse effects and encouraging results described in various reviews and meta-analyses (Fan et al., 2018; Kashiwagi et al., 2018; Salazar et al., 2018; Zebhauser et al., 2019).

NeuronUP: neurorehabilitation platform

The neuropsychological rehabilitation program aimed at rehabilitating hemineglect is based on the use of the NeuronUP rehabilitation platform, a platform designed for the rehabilitation and stimulation of cognitive functions.

We have chosen this platform because it has a large bank of activities that can be carried out both interactively and using pencil and paper. Its ease of use and great adaptability to the characteristics of each user allow the personalized intervention programs for each person to be designed easily and appropriately.

Nine specific exercises aimed at stimulating and rehabilitating hemineglect have been selected and combined across the 10 intervention sessions (4 tasks per session), each lasting 30 minutes. The platform configuration allows sessions to be scheduled in order to progressively increase task difficulty based on the participant’s achievements. Thus, in each session the difficulty of the activities is adjusted according to the previous day’s performance.

The ease of scheduling, the recording of users’ performance in each task and the extensive and novel bank of activities specifically designed to target certain cognitive functions make it possible to carry out the intervention sessions systematically and without design errors, which guarantees homogeneity in the application of the treatment to all participants.

tDCS-Neglect Project

To participate in the research project, participants must meet a series of requirements; among them we can mention:

• Have suffered a hemorrhagic or ischemic stroke in the right hemisphere.
• Time since the injury between 3 months and 12 months.
• Be over 18 years old.
• Have a neuroimaging study performed.
• No prior strokes.
• Functional capacity that allows them to remain seated and active for one hour.
• Right-handed.
• Demonstrate hemineglect on objective assessment tests.
• Signed informed consent by the affected person or their legal guardian.

Neuropsychological assessment and EEG

All participants undergo at the start of the study a neuropsychological assessment and an electroencephalogram (EEG). The neuropsychological assessment is aimed at identifying the presence of hemineglect and the severity of the symptoms, also assessing the functional impact of this disorder on daily functioning and the impairment or preservation of other cognitive functions, such as attention and working memory. The neuropsychological assessment and the EEG will be carried out three days before the start of the intervention with tDCS and NeuronUP. The same assessment protocol will be repeated three days after the end of the intervention, in order to analyze the cognitive improvements that may have occurred, changes in physiological measures (EEG), and the correlation between both measures.

Content

Participants are assigned to one of two intervention groups; the intervention program consists of 10 neuropsychological rehabilitation sessions with NeuronUP over two weeks (Monday to Friday). One of the groups (active group) receives neuropsychological rehabilitation for 30 min combined with active tDCS for 20 minutes (starting 5 min after the start of NeuronUP). The other group (placebo group) follows the same neuropsychological rehabilitation program but combined with placebo tDCS (called sham tDCS) for the same duration. In all cases, participants, evaluators and the neuropsychologists responsible for carrying out the intervention program are blind to the experimental conditions assigned, that is, they do not know to which group each participant has been assigned.

The novelty of this study lies in the combination of two tools aimed at the stimulation and improvement of a disorder with a high prevalence and serious repercussions on the person’s functional independence, such as hemineglect. The combination of both therapeutic approaches will enhance the improvement of hemineglect symptoms, so that the benefits will be greater than those achieved by the techniques separately.

In the following video we present a more detailed explanation of the project and its objectives.

Participation

The study is currently open to any person affected by a stroke who presents symptoms of hemineglect, meets the inclusion criteria mentioned and wishes to participate voluntarily in the study. Individuals or centers interested in participating can contact the lead researchers of the project:

Dr. Juan Pablo Romero

Email: [email protected]

Dr. Elena Muñoz Marrón

Email: [email protected]

This article was carried out by Begoña González, Elena Muñoz and Juan Pablo Romero. You can consult more projects of the research groups involved at: https://www.ufv.es/neurorrehabilitacion-dano-cerebral/

Bibliography

• Azouvi, P., Jacquin-Courtois, S., & Luauté, J. (2017). Rehabilitation of unilateral neglect: Evidence-based medicine. Annals of Physical and Rehabilitation Medicine, 60(3), 191-197. https://doi.org/10.1016/j.rehab.2016.10.006
• Bang, D.-H., & Bong, S.-Y. (2015). Effect of a combination of transcranial direct current stimulation and feedback training on visuospatial neglect in patients with subacute stroke: A pilot randomized controlled trial. Journal of physical therapy science, 27(9), 2759‐2761.
• Bikson, M., Grossman, P., Thomas, C., Zannou, A. L., Jiang, J., Adnan, T., Mourdoukoutas, A. P., Kronberg, G., Truong, D., Boggio, P., Brunoni, A. R., Charvet, L., Fregni, F., Fritsch, B., Gillick, B., Hamilton, R. H., Hampstead, B. M., Jankord, R., Kirton, A., … Woods, A. J. (2016). Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Brain Stimulation, 9(5), 641-661. https://doi.org/10.1016/j.brs.2016.06.004
• Chen, P., Hreha, K., Kong, Y., & Barrett, A. M. (2015). Impact of spatial neglect on stroke rehabilitation: Evidence from the setting of an inpatient rehabilitation facility. Archives of Physical Medicine and Rehabilitation, 96(8), 1458-1466. https://doi.org/10.1016/j.apmr.2015.03.019
• Colombo, A., De Renzi, E., & Gentilini, M. (1982). The time course of visual hemi-inattention. Archiv Für Psychiatrie Und Nervenkrankheiten, 231(6), 539-546. https://doi.org/10.1007/BF00343997
• Edwards, D., & Fregni, F. (2008). Modulating the healthy and affected motor cortex with repetitive transcranial magnetic stimulation in stroke: Development of new strategies for neurorehabilitation. NeuroRehabilitation, 23(1), 3-14.
• Fan, J., Li, Y., Yang, Y., Qu, Y., & Li, S. (2018). Efficacy of Noninvasive Brain Stimulation on Unilateral Neglect After Stroke: A Systematic Review and Meta-analysis. American Journal of Physical Medicine & Rehabilitation, 97(4), 261-269. https://doi.org/10.1097/PHM.0000000000000834

• Fasotti, L., & van Kessel, M. (2013). Novel insights in the rehabilitation of neglect. Frontiers in Human Neuroscience, 7, 780. https://doi.org/10.3389/fnhum.2013.00780
• Hummel, F. C., & Cohen, L. G. (2006). Non-invasive brain stimulation: A new strategy to improve neurorehabilitation after stroke? The Lancet Neurology, 5(8), 708-712. https://doi.org/10.1016/S1474-4422(06)70525-7
• Jehkonen, M., Laihosalo, M., & Kettunen, J. E. (2006). Impact of neglect on functional outcome after stroke: A review of methodological issues and recent research findings. Restorative Neurology and Neuroscience, 24(4-6), 209-215.
• Kalra, L., Perez, I., Gupta, S., & Wittink, M. (1997). The influence of visual neglect on stroke rehabilitation. Stroke, 28(7), 1386-1391.
• Karnath, H.-O., Rennig, J., Johannsen, L., & Rorden, C. (2011). The anatomy underlying acute versus chronic spatial neglect: A longitudinal study. Brain: A Journal of Neurology, 134(Pt 3), 903-912. https://doi.org/10.1093/brain/awq355
• Kashiwagi, F. T., El Dib, R., Gomaa, H., Gawish, N., Suzumura, E. A., da Silva, T. R., Winckler, F. C., de Souza, J. T., Conforto, A. B., Luvizutto, G. J., & Bazan, R. (2018). Noninvasive Brain Stimulations for Unilateral Spatial Neglect after Stroke: A Systematic Review and Meta-Analysis of Randomized and Nonrandomized Controlled Trials. Neural Plasticity, 2018. https://doi.org/10.1155/2018/1638763
• Katz, N., Hartman-Maeir, A., Ring, H., & Soroker, N. (1999). Functional disability and rehabilitation outcome in right hemisphere damaged patients with and without unilateral spatial neglect. Archives of Physical Medicine and Rehabilitation, 80(4), 379-384.
• Ladavas, E., Giulietti, S., Avenanti, A., Bertini, C., Lorenzini, E., Quinquinio, C., & Serino, A. (2015). A-tDCS on the ipsilesional parietal cortex boosts the effects of prism adaptation treatment in neglect. Restorative neurology and neuroscience, 33(5), 647‐662. https://doi.org/10.3233/RNN-140464

• Kinsbourne, M. (1977). Hemi-neglect and hemisphere rivalry. Advances in neurology, 18, 41-49.
• Luukkainen-Markkula, R., Eng, N., & Tarkka, I. (2014). Recovery from neglect after right hemisphere stroke. International journal of neurorehabilitation, 1. https://doi.org/10.4172/ijn.1000103
• Paolucci, S., Antonucci, G., Grasso, M. G., & Pizzamiglio, L. (2001). The role of unilateral spatial neglect in rehabilitation of right brain-damaged ischemic stroke patients: A matched comparison. Archives of Physical Medicine and Rehabilitation, 82(6), 743-749.
• Salazar, A. P. S., Vaz, P. G., Marchese, R. R., Stein, C., Pinto, C., & Pagnussat, A. S. (2018). Noninvasive Brain Stimulation Improves Hemispatial Neglect After Stroke: A Systematic Review and Meta-Analysis. Archives of Physical Medicine and Rehabilitation, 99(2), 355-366.e1. https://doi.org/10.1016/j.apmr.2017.07.009
• Wilkinson, D., Sakel, M., Camp, S.-J., & Hammond, L. (2012). Patients with hemispatial neglect are more prone to limb spasticity, but this does not prolong their hospital stay. Archives of Physical Medicine and Rehabilitation, 93(7), 1191-1195. https://doi.org/10.1016/j.apmr.2012.01.010
• Yi, Y. G., Chun, M. H., Do, K. H., Sung, E. J., Kwon, Y. G., & Kim, D. Y. (2016). The Effect of Transcranial Direct Current Stimulation on Neglect Syndrome in Stroke Patients. Annals of Rehabilitation Medicine-Arm, 40(2), 223-229. https://doi.org/10.5535/arm.2016.40.2.223
• Zebhauser, P. T., Vernet, M., Unterburger, E., & Brem, A.-K. (2019). Visuospatial Neglect-a Theory-Informed Overview of Current and Emerging Strategies and a Systematic Review on the Therapeutic Use of Non-invasive Brain Stimulation. Neuropsychology Review, 29(4), 397-420. https://doi.org/10.1007/s11065-019-09417-4

If you liked this post about rehabilitation of hemineglect after stroke, you might be interested in these NeuronUP articles.

“This article has been translated. Link to the original article in Spanish:”
La rehabilitación de la heminegligencia tras el ictus