Introduction

Spatial neglect syndrome, a behavioral disorder, also known as unilateral or hemineglect syndrome, is a disabling condition that often presents with diagnostic difficulties even for specialists familiar with this condition.[1] This hemineglect syndrome classically presents as non-dominant (often left-sided) spatial disorientation after a pathological event in the right cerebral hemisphere, classically the right posterior parietal cortex. Spatial neglect does not necessarily limit involvement to sensory and motor impairment, but can also affect other components like perceptual, representational, visuospatial, behavioral deficits, etc. The most challenging aspect of this illness is the frequent abnormal awareness of the patient regarding the deficit termed anosognosia and the presence of emotional dysfunction.[2] 

Neglect is a heterogeneous syndrome due to variations in the location and extent of brain damage. This interhemispheric imbalance causes the left hemisphere to become more active after the right hemisphere lesion, which results in attention diversion and eye movements towards the right side. The presence of spatial neglect indicates a severe prognosis in terms of the long-term independent functioning of the patient.[3] 

Clinicians can estimate the severity of this unilateral neglect using the Kessler Foundation Neglect Assessment Process (KF-NAP) or Conley Scale scores.

Etiology

A structural and functional disturbance in the brain cause spatial biasing.[4] The primary pathological process responsible for this neuropsychological disorder is a hemispheric stroke, particularly involving the non-dominant cerebral hemisphere, which is often the right cerebral hemisphere. Neglect is mainly due to the occlusion in the right middle cerebral artery territory that can cause disorientation in around 80% of the patients in the acute stage.[5] 

Other common causes are traumatic brain injury, neoplasia, and aneurysms formation in the cerebral circulation. Neurodegenerative diseases rarely cause hemineglect syndrome.[6]

Epidemiology

Although the incidence rate of left-hemispheric strokes is 54%, greater than right-hemispheric, which is 43%, the occurrence of spatial neglect is disproportionately more following a right-sided stroke.[7] The overall incidence of hemineglect disorder is up to 82% in post-stroke patients, with the involvement of around 50% of the individuals on average.[8][9] Age shows a correlation in patients with neglect following a stroke, unlike the handedness or the gender differences.[2] 

A case study reported the majority of patients of neglect above 65 years of age and fewer patients of neglect below the age of 65 years. Individuals with low socioeconomic status and White race reportedly show a strong association with spatial neglect.

Pathophysiology

Neglect disorder usually develops due to occlusion of cerebral blood flow, especially the main trunk of a right middle cerebral artery, the primary source of blood supply for the right-sided cerebral cortex. Commonly responsible areas of the right hemisphere are the right posterior parietal cortex with particular involvement of the inferior parietal lobe (IPL) or temporoparietal junction(TPJ). Gaze disturbance and anosognosia usually involve the perisylvian regions of the right hemisphere; however, biased line bisection and extinction are due to the involvement of posterior-inferior damage and the temporoparietal junction involvement.[10] 

Less commonly involved areas of the cerebral cortex are the superior temporal cortex and frontal lobe. In damage to subcortical regions, neglect can develop through indirect effects on cortical regions. Predominantly involved part of subcortex in causing neglect disorder is superior longitudinal fasciculus, while basal ganglia, thalamus, and cingulate cortex are least commonly involved.[11] The heterogenous symptoms present due to varying involvement of posterior cortical, frontal, subcortical, and white matter damage.

History and Physical

A detailed history regarding the previous cerebrovascular accident with underlying risk factors e.g., uncontrolled hypertension or diabetes, medication non-compliance, personality disorders, seizures/epilepsy, migraines, balance disorders, etc. should be obtained carefully in patients with suspected post-stroke spatial neglect syndrome. Since patients do not complain of deficits due to anosognosia, symptoms are commonly reported by family members or caregivers. Reported findings include behavioral changes, inability to dress, or use the contralateral limb.

Spatial neglect can affect the following aspects of spatial processing:

1. Perception-attention neglect: People with neglect having no disorder of sensation may still fail to perceive events on the neglected side.
2. Motor intentional aiming deficits: Patients may exhibit difficulty in initiating or performing movements on the contralesional side even when the motor system of the neglected side is intact.
3. Representational neglect: Also known as imagery neglect, first reported in an experiment by Bisiach and Luzzatti in 1978. In this scenario, the patient will have a defective left-sided internal mapping of scenes or objects.

A patient can have the following behavioral changes: 

1. The patient may have anosognosia, which is the unawareness of the deficit.
2. Self-neglect: The patient will perform all tasks from the non-neglected right side due to unawareness of his left side of the body, e.g., asymmetric shaving, grooming, etc.
3. Anosodiaphoria: this is an unconcerned behavior about the deficit due to emotional dysfunction secondarily to the involvement of the limbic system in the right cerebral hemisphere stroke. Hyperarousal is also observable in neglect disorder.

On examination, the patient may exhibit any of these following signs:

1. After the stroke, the bed-ridden patients look away from the right side. The patient in a wheelchair will have difficulty in navigating towards the left side.
2. Allochiria: This is an illusory visual phenomenon in which patients with neglect will only respond to stimuli presented to the right side of their body as if it had been to the other side while neglecting the left sided-stimuli. When one approaches such patients from the left side, they respond looking at the right side; a phenomenon also labeled as allesthesia.[12]
3. Somatoparaphrenia: The patient develops a delusional belief that the neglected side of the body belongs to someone else.[5] At times, it can cause grave consequences when such patients deny life-threatening conditions, e.g., left-sided chest pain due to myocardial infarction.
4. The patient may have peripersonal or extrapersonal neglect, depending on the inability to reach out in the space within the reaching distance or outside that distance.

Evaluation

Evaluation of patients with suspected hemineglect syndrome consists of complete neurological examination, lab evaluation, and imaging studies.

Any of the following bedside methods can provide a neurological examination of these patients: 

1) Cancellation Test: This is a visual stimulation test in which patients view a piece of paper having scattered lines all over, and they are asked to cross or circle all the lines. In the end, the patient will only cross lines on the non-neglected side, leaving behind the affected side.[13]

2) Line Bisection Test (LBT): A long line is drawn on the paper, and the patient is asked to mark the center of the line. Instead of the center, the patient will direct the line more towards the right side, ignoring the left side of the line. The performance time of the line bisection test has a significant association with hemispatial neglect prognosis.[14]

3) Drawing/Copying Test: Ask the patient either to draw something from his memory or to copy the given task.

4) Multitasking/Double-Simultaneous stimulation: The presence and severity of contralesional neglect and extinction can be overlooked depending on standard single testing procedures such as LBT, copying, etc. because patients can easily compensate for their deficits.[15] Extinction, which is an associated symptom of neglect, can be tested by asking the patient to count fingers in both hemifields.

5) Reading Test: A person with spatial neglect will read only the right side, which is the non-neglected side, while ignoring the left side, e.g., ask the patient to read "460225", the patient will read-only "225".

Lab investigations can help to exclude other causes of dementia, depression, and stroke include vitamin-B12 level, homocysteine level, Thyroid function tests (TSH, T3, T4), complete blood counts (CBC), comprehensive metabolic panel (CMP), glycosylated hemoglobin (HbA1c).

Structural brain abnormalities like acute ischemic stroke, brain tumor, subdural hematoma, must be evaluated with computed tomography (CT) head or magnetic resonance imaging (MRI) of the brain. CT head is readily available and is the first-line test in an emergency. A brain MRI is more sensitive and can provide more details of the etiology and is necessary when available, especially when the CT head is non-diagnostic.   

CT angiography or MR angiography is useful when cerebral aneurysms or vascular malformations are suspected. Conventional angiography has a higher sensitivity but is more invasive must be used on a case by case basis.  

Differential Diagnosis

Following differentials must be considerations in a patient with spatial neglect.

1. Ataxic hemiparesis which presented with weakness and ataxia on the same side
2. Gerstmann syndrome which presents with acalculia, finger agnosia, agraphia, and left-right disorientation
3. Balint syndrome presents with an inability to visualize more than one object in the visual field simultaneously and failure to reach an item with his right hand but able to do so with the left hand.
4. Anton syndrome of cortical blindness
5. Primary somatosensory or motor disturbances.
6. Other common non-neurological conditions that can mistakenly merit consideration as a reason for neglect include depression, conversion disorder, vestibular dysfunction, etc.

Prognosis

The prognosis of neglect patients greatly depends on the timely identification of this disorder in patients because about 80% of patients are reportedly initially undiagnosed.[1] Hence the most important aspect step in having a better outcome is the accurate diagnosis of neglect in patients, especially in post-stroke individuals.

Identification tests can also give a clue regarding prognostic index of such candidates, for instance, the cancellation test can predict the mortality and functional activity of neglect patients six months after the stroke according to the results of Albert's experiment.[20] 

Patients with neglect can often recover from the post-stroke acute phase due to reperfusion and resolution of cerebral edema, increasing the activity of left prefrontal and right parietal regions.[21] At the end of 12 weeks, neglect is present in 17% of right-brain lesioned patients and 5% of left-brain lesioned patients according to the NIH scale.[22] This 23% of the affected individuals have increase duration for a hospital stay along with increase morbidities due to repeated falls. Occupational functioning also significantly decline in patients having neglect with anosognosia.

Complications

Hemispatial Neglect(HSN) results in multiple complications not only for the patients but for the caretakers as well.

1. Occupational insufficiency. HSN makes patients unable to perform their duties because of visual and motor perception deficits in the contralesional field. 
2. A tendency to develop delirium increases in post-stroke patients with neglect. A study reported up to 48% of patients who have had a stroke develop delirium.[23]
3. Safety issues can arise because of the inability of a patient to articulate properly or to act spontaneously in emergency situations making such individuals unable to drive on the road.
4. Spatial neglect lengthens the stroke survivors' recovery time to be an independent person again that results in increasing caregivers' stress levels.[24]

Deterrence and Patient Education

Hemineglect syndrome is a disabling condition with high morbidity and mortality. Hence the health care providers need to educate the other healthcare team members and caregivers regarding different aspects of neglect with its probable side effects in routine functioning. Absence of activity, speech, and emotions may mimic the situation as depression and lack of motivation, so thorough counseling sessions should be set up for the immediate family members involved in patient care. It is crucial to make the patients, families, and caregivers realize that some functional and navigational problems can persist even after the recovery.

Enhancing Healthcare Team Outcomes

Healthcare outcomes can be enhanced by sustained coordination and communication between health professionals team, which consist of physicians, nurses, physical and occupational therapists, neuropsychologist, social workers, language therapists, and dieticians. Maximum effective rehabilitation is achievable only when there is no communication gap, and when a strong doctor-patient relationship exists. Lack of coordination makes it unlikely to achieve full recovery.[25]