Spatial Neglect 

Spatial neglect is a behavioral syndrome occurring after brain injury. Spatial neglect involves the inability to report, respond, or orient to stimuli, generally in the contralesional space.^[1] The authors have suggested that spatial neglect should also be defined by functional disability.^[2] The deficit must not be fully attributable to primary sensory deficits (eg, hemianopia) or motor disturbance (eg, hemiparesis).

Treatment for spatial neglect focuses on cognitive rehabilitation that uses specific exercises and alterations to the patient's environment.

Despite the fact that speech and language, memory, and other cognitive abilities may be spared in brain-injured patients with spatial neglect, the prognosis for recovery of independent function in patients with persisting spatial neglect is worse than in those with seemingly more disabling deficits in these other abilities.^[3] Even global aphasia and right hemiparesis may not have as great an effect on the ability to become independent.^[4]

Although patients may recover from spatial neglect, they often remain severely disabled. The reasons for the persistent disability are poorly understood, although this dissociation might be explained by an overly narrow clinical definition for the presence of spatial neglect. Daily life functions are often performed under more challenging conditions than is the case for formal neuropsychological testing (eg, distractions, need for dual or multitasking, continuous dynamic computations using output from previous operations, need for self-initiation and self-organization) and may involve larger areas of space than a paper-and-pencil task on a tabletop (eg, navigating in an airport or mall, playing baseball, driving).

Spatial neglect also encompasses a cluster of symptoms affecting several areas of vital importance in daily life and is associated with other cognitive dysfunction, such as emotional processing dysfunction and abnormal awareness of deficits (anosognosia for hemiplegia [may occur in the hyperacute phase of right hemispheric stroke in as many as 32% of patients, about 18% after 1 week and 5% after 6 months^[5] ] and anosodiaphoria), which may affect independence.^[1]

Patient education

Family members involved in patient care should be well educated in the various aspects of neglect and its implications for day-to-day functioning. Family members and patients should be made aware that even after seeming recovery of spatial neglect, some patients may have functional problems, including difficulty with complex navigating in familiar and unfamiliar environments and safe driving.

Causes of spatial neglect include stroke, traumatic brain injury, brain tumors, and aneurysm. Rarely, neurodegenerative diseases can cause neglect symptoms.^{[6, 7]}

People with injury to either side of the brain may experience spatial neglect, but neglect occurs more commonly in persons with brain injury affecting the right cortical hemisphere, which often causes left hemiparesis.^[8]

Spatial neglect is more commonly associated with lesions of the inferior parietal lobule or temporoparietal region, superior temporal cortex, or frontal lobe. Less common are lesions of the subcortical regions, including the basal ganglia, thalamus, and cingulate cortex.^{[1, 9, 10, 11]} Spatial neglect may be more common and persistent after cortical, rather than subcortical, lesions.^[8]

Because different neuroanatomic systems may be dysfunctional with spatial neglect, different neuropsychological mechanisms, as follow, may explain the process of this disorder:

• Perception-attention - In the absence of primary sensory deficits, people with spatial neglect may have disordered awareness of events occurring on the neglected side^[1]
• Imagery/representation - Even when no external stimuli are present, people with spatial neglect may have difficulty maintaining an internal map or image or other spatial knowledge pertaining to the environment, objects, body, or other reference frames

Additional dysfunctions that may be found in individuals with spatial neglect include the following:

• Self-monitoring - People with spatial neglect may be unaware of their deficit (anosognosia) or may be unconcerned about it (anosodiaphoria)
• Emotional processing - After a right-hemisphere stroke, individuals may have difficulty making appropriate emotional facial expressions and may lack normal affect or vocal intonation (at times, these signs can be mistaken for poststroke depression); patients may also have difficulty representing emotional knowledge (disordered emotional semantics) or understanding emotional information presented via others' vocal prosody or facial expressions
• Arousal - Hypoarousal may be associated with spatial neglect
• Motor intentional deficits - These deficits include motor neglect and premotor neglect; people with spatial neglect may have trouble with activating or directing actions into portions of space; they may also be slow to act and may not persist
• Personal neglect - Individuals may not normally attend to the left side of their body

Reported overall frequency of spatial neglect in the United States is estimated to be anywhere from 13-81% in people who have had a right-hemisphere stroke, although 2 studies reported an overall rate of approximately 50%.^{[8, 12]} The frequency of spatial neglect may increase with the size of the lesion at presentation and at 3 months after injury.^[8] International frequency of spatial neglect is not known.

No evidence currently indicates that spatial neglect is more common in either gender.^[13] Spatial neglect may be more common in older individuals after stroke than it is in younger individuals, according to some preliminary evidence.^{[8, 14, 15, 16]}

Although neglect may be seen at baseline, obvious symptoms improve rapidly within the first few days.^[8] The potential mechanisms include reperfusion of the penumbral area and resolution of cytotoxic edema and other factors.

Most patients with neglect show early recovery, particularly within the first month,^[17] and marked improvement may be seen within 3 months^[8] .

Patients who demonstrate symptoms of spatial neglect would be expected to benefit from referral for outpatient treatment with speech therapy, occupational and physical therapy,^[18] neuropsychological therapy, or a combination of these referrals, even if obvious signs of spatial neglect appear to have abated, because spatial bias may be present in functional tasks that cannot be detected by interacting with the patient briefly at the bedside.

In approximately 10% of patients, classic (more severe) symptoms of spatial neglect persist after 6 months or longer. In these individuals, the deficit may be regarded as chronic neglect. Patients demonstrating persistent symptoms, when present with other impairments or disabilities, may benefit from intensive inpatient rehabilitation and may need to live under supervision if the patient will otherwise not be safe.

Whether people with spatial neglect fully recover is controversial. Although symptoms abate in most patients in weeks to months^[14] , patients are not usually evaluated on dynamic tasks in the presence of distraction; subtle and functionally important bias may persist.

When persistent, spatial neglect is an unfavorable sign for overall improved prognosis.^[3] Neglect syndrome predicts a poor outcome in persons with right-hemisphere stroke.^[12]

Spatial neglect may greatly increase morbidity and the risk of acute and chronic complications of stroke (eg, hip fracture). It is associated with a longer acute hospital stay.^[19]

Patients with neglect need to be monitored because they may be more prone to falls or left-sided wheelchair collisions.^[20] Patients may require sitters, vest restraints, gait belts, or other interventions to prevent falling out of bed, for which they are at high risk.

Whether any acute stroke management strategies can decrease the risk of poststroke spatial neglect is currently unknown, although animal studies suggest that factors as fundamental as ambient room light may affect the development of spatial neglect symptoms.^[21]

Spatial neglect is commonly observed after cerebral infarction or hemorrhage. Because of associated abnormal self-monitoring (anosognosia), individuals usually do not report attention or perceptual problems. Thus, the disorder is usually detected via clinical observation and testing. A complete neurologic evaluation by a thorough and knowledgeable clinician may be needed to document the presence of the syndrome and even of the underlying stroke that caused it; a cursory examination in a nonaphasic patient would be unlikely to demonstrate the neglect syndrome.

Spatial neglect symptoms are often first observed by caregivers or therapists, who may note personal neglect (failure to groom or clothe the contralesional side) or motor neglect (may not use the contralesional limb despite adequate motor strength or may not explore left space). The most severe cases of spatial neglect may be diagnosed by simple bedside observation, and more moderate cases may be diagnosed based on findings from a complete neurologic examination that includes neurobehavioral testing. The following observations may be made:

• In acute care settings, the position of the patient in bed or in a wheelchair (lying with the head and eyes turned to the extreme ipsilesional side, usually the right) may first arouse suspicion of the presence of spatial neglect
• A patient may have difficulty maintaining a normal posture (may be tilted or crooked in the bed); the contralesional leg may dangle off the bed
• When approached from the left, patients may bizarrely orient and reply to the right, away from the person addressing them (allesthesia)
• People with spatial neglect may navigate their wheelchairs or ambulate in a rightward-biased manner; alternately, they may collide with doorways or objects on the left
• Spatial neglect of perceptual-attentional, representational, or motor-intentional types may affect several regions of contralesional space; patients may have problems with near space, within reaching distance (peripersonal neglect), or space beyond reaching distance (extrapersonal neglect)
• Patients with spatial neglect may deny ownership of their contralateral limb, stating that it belongs to someone else (asomatognosia); they may express dislike of their paralyzed limb (misoplegia)
• Patients may deny a neurologic problem (anosognosia), underestimate the severity or implications of their deficit, or fail to express sadness or anger about their difficulties and losses (anosodiaphoria); anosognosia particularly impairs participation in rehabilitation

Conditions to consider in the differential diagnosis of spatial neglect include the following:

• Complex partial seizures
• Cortical basal ganglionic degeneration
• Multiple sclerosis
• Wallenberg (lateral medullary stroke) syndrome - Lateropulsion may produce an abnormal bed posture
• Other stroke syndromes
• Primary visual or motor systems abnormality - Such as cortical blindness or spinal cord abnormality
• Vestibular abnormality
• Posterior cortical atrophy - A neurodegenerative disorder that can be associated with spatial neglect
• Conversion disorder
• Migraine accompaniment

Laboratory tests are determined based on the neurologic disorder causing the cortical or subcortical-cortical deficit (eg, stroke, tumor, aneurysm) and vary accordingly.

Check vitamin B-12 levels, thyrotropin levels, and total thyroxine levels if memory impairment accompanies spatial neglect; perform these tests for all patients, even if diagnosed with an acute neurologic syndrome. Elevated homocysteine levels should not be interpreted as idiopathic in stroke patients unless vitamin B-12 deficiency has been excluded as a possible cause.

Check rapid plasma reagent values in patients with memory disorder, especially when associated with stroke, to evaluate for potentially treatable secondary conditions. Although false-negative and false-positive results occur, false-positive results may also be clinically relevant (eg, for connective-tissue disease).

Computed tomography (CT) scanning or magnetic resonance imaging (MRI) is indicated even if the clinical picture is otherwise entirely consistent with a right-middle cerebral artery stroke syndrome, because subdural hematomas, brain tumors, or other mass lesions occasionally mimic a stroke.

Contrast-enhanced MRI is generally nontoxic and increases the sensitivity of the technique for detecting the above diagnostic confounds. CT scanning alone is adequate to detect hemorrhage, but it is insufficiently sensitive to detect some other lesions seen with MRI. Diffusion-weighted MRI distinguishes acute ischemia from chronic infarction.

Magnetic resonance angiography, conventional angiography, or functional imaging, such as single-photon emission CT or positron emission tomography (PET) scanning, may be required for the management of stroke, brain tumor, or another primary brain disorder causing spatial neglect.

A complete neurologic examination needs to be performed. This must include a complete test of higher cortical function at the bedside. Tests of right and left hemisphere function should be performed. Specific tests for neglect often include the following:

• Line bisection test
• Letter cancellation test
• Drawing and copying
• Reading and writing
• Sensory tests - Involving double-simultaneous stimulation for extinction in the visual, auditory, somatosensory, or motor modalities

Performing more than 1 screening behavioral test is recommended to increase the sensitivity of detecting neglect. Patients who perform abnormally on one test but who do not show abnormal performance on other tasks may still have functional impairment as a result of neglect-related symptoms.^[22]

Line bisection test

Line bisection tests are easy, universally available bedside tests to screen for the presence of hemispatial neglect that take 15 seconds or less to perform. (See the image below.)

Detailed assessment of a patient's ability to bisect lines is ideally accomplished using several trials with different line lengths greater than 22 cm. In the motor line bisection task, use also vertical lines and radial lines.^[23]

Neglect is also more apparent when the lines are placed in the contralesional body or head space.^[23]

The lines should be as long as possible (eg, the entire span of a page) because neglect is more apparent when longer lines are used.^[24]

Cancellation task

The ability to cancel an array of lines or other stimuli may be used.^[25] Letter cancellation, symbol cancellation, or other target cancellation from an array can be tested. (See the image below.)

Double-simultaneous stimulation

Testing for extinction using double-simultaneous stimulation is performed because patients may be able to detect single stimuli on the right and left hemifields but not double-simultaneous stimuli in both hemifields.

Patients with spatial neglect may not perceive a contralesional stimulus when it is simultaneously presented with an ipsilesional stimulus. This may occur simultaneously with visual, tactile, or auditory modalities.^[1]

At the bedside, this can be tested by asking the patient to count fingers presented to both hemifields, snapping fingers at both ears, or touching both hands. Extinction cannot be tested if a patient's ability to detect a single stimulus is impaired.

Drawing

Although time consuming, testing the ability of the patient to draw, either by having him or her draw from memory (eg, draw-a-person task) or by having the patient copy the examiner's production (see the image below), may be one of the most sensitive means of detecting spatial neglect.

Additional tests

Other bedside tests may be carried out. For example, the patient can be observed to see if he or she has evidence of personal (body) neglect (eg, symmetrical shaving, grooming).

Reading assessment can be useful, particularly for planning occupational and vocational rehabilitation. When reading English, patients with spatial neglect may not begin reading at the left margin; rather, they may start in the middle of the page. When asked to identify single words, they may omit left-sided letters so that "blueberry" may be read as "berry" (neglect dyslexia).

Informal anosognosia testing is performed by asking the patient about his or her presentation to the hospital and the symptoms. For example, questions may include the following: "Are you weak anywhere?" or "Do you have any problems with your vision or with detecting objects?"

Distinguish neglect and hemianopia (which may coexist) by directing the patient's gaze into the preferred (eg, right) hemispace. In many people with spatial neglect, the ability to detect visual stimuli in the contralesional retinal hemifield improves when gaze is directed into the non-neglected hemispace (eg, when the patient looks to the extreme right and a stimulus is presented a few degrees to the right of the body midline, in the left retinal hemifield). These patients are less likely to have true hemianopia.^[26]

Treatment of spatial neglect includes specific cognitive rehabilitation measures that target each type of deficit. However, although geriatric individuals may be at higher risk for spatial neglect, behavioral treatments may not be as effective for these patients. Unfortunately, special management strategies for people older than 65 years with spatial neglect are not yet available.

Perceptual deficit rehabilitation

Environmental modification

Perceptual deficit rehabilitation may be performed via environmental modification. The patient's bedside environment may be oriented leftwards and hence make the patient perceive his or her left side.

Interventions used to attempt to shift the representation of space rightward include the following:

• Prism adaptation^{[27, 28]}
• Caloric stimulation^{[29, 30]}
• Trunk rotation treatment^[31]
• Optokinetic stimulation^[32]
• Vibration of left posterior neck muscles^[31]

These may act at a representational level, shifting the representation of space to the neglected side. Eye patching to increase leftward orientation has also been attempted as a treatment for neglect.^{[33, 34]}

Cueing

Perceptual deficit rehabilitation may be performed via cueing. Scanning training attempts to encourage patients to direct their gaze to the neglected side and to scan their environment to the left with verbal cueing.

Other methods to improve awareness of the neglected side include cueing patients to find a red line or other stimulus placed by therapists on the left margin of a page.

Recommendations for clinical practice in cognitive rehabilitation made in 2000 noted visuospatial scanning as a practice parameter in persons with visual neglect after a right-hemisphere stroke.

Unawareness rehabilitation

Unawareness rehabilitation may be performed via environmental modification and family education. For example, one modification might include positioning the patient's chair or bed asymmetrically in the room. (It is not known whether the chair or bed should be positioned so that the room is in the preferred or neglected space—both may be theoretically helpful.)

Family members may simplify the visual environment by setting the table with as few items as possible to improve attention to food and utensils.

Emotional processing rehabilitation

Emotional processing rehabilitation may be performed through the careful education of the caregivers or family. When present, underlying depression needs to be treated.

Hypoarousal therapy

Hypoarousal treatment using dopaminergic drugs (eg, bromocriptine) has been used to treat neglect as part of a treatment strategy that targets arousal and attention deficits associated with neglect.^[35] Patients should be reevaluated while they are on medication, because paradoxical effects have been reported.^[36]

The dopamine agonist apomorphine improved neglect in one study.^[37] Other dopaminergic agents or stimulants may be useful but have not been well studied.

Hypoarousal rehabilitation has been attempted by training patients to sustain attention by self-alerting.^[38]

Poststroke patients with severe hypoarousal accompanying spatial neglect, or severe anosognosia, may require transfer to subacute care, because they may be unable to tolerate or cooperate with the usual recommendation of intensive acute rehabilitation.

Motor bias rehabilitation

Motor bias rehabilitation is performed by having patients use their extremity in the left hemispace. A form of constraint-induced therapy, in which the nonparetic limb is restrained and motor cueing is used for the left hand, may also address motor bias.

Personal neglect rehabilitation

Personal neglect rehabilitation is addressed mainly by occupational therapists in the course of addressing the activities of daily living and may involve direct verbal, visual, or tactile cueing.

Consultation with a skilled neuro-optometrist may be considered in the presence of hemianopia. A detailed bedside examination is preferred over automated methods of assessing visual-field deficits.

Consultation with a neuropsychologist can be helpful for family and caregiver counseling and for transition to long-term stages of recovery and potential community reintegration, as well as for dealing with issues of psychological adjustment by the patient, who may have intact emotional reactions but an impaired ability to communicate emotionally.

The use of dopaminergic or other medications for spatial neglect, although an exciting and developing area,^[36] has not yet become standard care for this disorder. An established practice, however, is to withhold anticholinergic medications, antidopaminergic medication (eg, for gastrointestinal indications), sedatives, and hypnotics in these patients unless absolutely necessary, because these agents may adversely affect the symptoms of spatial neglect and eventual functional recovery.

Similarly, phenytoin is relatively contraindicated. Patients taking the above medications should be carefully monitored and their spatial neglect symptoms should be periodically reevaluated.

No current clinical literature supports a benefit related to the use of modafinil or cholinesterase inhibitors in patients with spatial neglect. Neither treatment would be expected to specifically remediate attentional asymmetry, and improving attention and orienting of intact brain systems might actually worsen behavioral asymmetry.^[36]

The most important issue that may have legal implications in cases of spatial neglect is driving. Patients with spatial neglect may not be allowed to drive, for their safety and the safety of the others. Unfortunately, how people with driving disability can be identified is not clear, short of an on-road standard driving evaluation by consultation through a clinical driving program.

Patients who have had acute spatial neglect, even if the symptoms appear to have resolved, should undergo this evaluation before returning to driving.

Patients should undergo an occupational/vocational rehabilitation evaluation before returning to work that involves handling machines or tools that may cause injury to self or others.

Dangerous tools, firearms, and other environmental risks should be removed from the homes of patients with more severe deficits who are homebound but are not constantly supervised. The authors have observed a number of accidents in the home and workplace when patients and families were not compliant with management recommendations.