Visual neglect in posterior cortical atrophy

Posterior cortical atrophy (PCA) is a rare, early-onset neurodegenerative disease, characterized by a progressive impairment of higher order visual functions out of proportion to other cognitive disabilities [1] and occipito-parietal damage, which is often more severe in the right hemisphere [2, 3]. Asymmetric parietal damage might predict a frequent occurrence of visual neglect and related disorders such as visual extinction in PCA patients. Despite this, neglect and extinction appear to be relatively rare findings in PCA [4, 5] mainly observed late in the course of the disease [1]. However, neglect may easily pass undetected if not assessed with specific tests [6]. Thus, a study employing specific neglect tests [7] revealed signs of left-sided neglect in six patients, and of right-sided neglect in one patient out of a group of 15.

Patients with visual neglect are impaired in responding to events occurring on the side opposite to a brain lesion [8, 9], mainly affecting the right temporo-parietal region and its connections with the frontal lobe [10, 11]. Therefore, in stroke patients left-sided neglect is more frequent and severe than right-sided neglect [12]. Patients with left brain damage may also show signs of right-sided neglect, albeit more rarely and in a less severe form [12]. Concomitant damage to the right hemisphere might be important for the emergence of right-sided neglect [13]. Neglect often co-occurs with visual extinction, the failure to detect contralesional stimuli on bilateral presentation with preserved detection of the same stimuli when presented in isolation[14] or with primary visual field defects, such as homonymous hemianopia[15]. Diagnosis is important, because neglect has a dramatic impact on patients' functional disability [16], requires specific rehabilitation [17] and increases family burden [16].

In this prospective study, we aimed at establishing the side, the frequency and the severity of visual neglect, visual extinction, and primary visual field defects in an unselected sample of 24 PCA patients, by using standardized visuospatial tests [18].

Visual neglect can be difficult to assess in PCA, because of its frequent association with deficits of visual perception, such as visual agnosia and simultanagnosia. This may account for previous findings [4, 5], based on clinical examination, that neglect rarely occur in PCA. Despite this, visual neglect and visual extinction were frequently observed in the present PCA patients when using specific tests. The use of more extensive neglect batteries [6, 22] might further increase the frequency of observation of neglect in PCA. On the other hand, visual neglect may contribute to PCA patients' impaired performance on other tasks implicating a visuospatial component, such as the Corsi block test, text reading, sentence writing and copy of the Rey figure.

Three patients of our series showed clinical signs of left homonymous hemianopia, a very rare finding in neurodegenerative conditions [23]. However, severe neglect may induce lack of responses even for isolated left-sided stimuli, such as those used in the clinical confrontation method, and be mistaken for field loss. This does not seem to be the case for the present patients 10-12, who had severe neglect on line bisection (as typically found in patients with an association of neglect and hemianopia, see ref. 15), but not on the bells test, where they were able to detect between 53% and 80% of left-sided targets (see Table 2). In any case, to confirm the unexpected finding of left hemianopia in PCA, future studies should add visual field perimetry or visual evoked potentials to the standard clinical examination of visual functions.

As in patients with focal lesions [12], left-sided neglect was generally more severe than right-sided neglect. These results are consistent with reports of asymmetries in cortical degeneration in PCA, with the right hemisphere often being more affected than the left hemisphere [2, 3]. Non-lateralized deficits of attention and working memory, resulting from injury of right-hemisphere structures like the right inferior parietal lobe [24], may contribute to the presence and severity of neglect. Such structures are commonly damaged in PCA and may also account for the emergence of the neglect syndrome in this neurodegenerative condition. In contrast to evidence coming from stroke patients [12] and from previous results on neglect in PCA [7], right-sided neglect resulted more frequently in PCA than in patients with focal damage to the left hemisphere, especially for line bisection (29% of pathological performance in our sample vs. 6.4% in a previous study [12] using similar stimuli, although a direct comparison is difficult given the differences in sample sizes). Such a finding is in line with evidence that damage of both hemispheres, as expected in PCA [2, 3], is more likely to cause signs of right-sided neglect than unilateral damage of the left hemisphere [13], and it is consistent with the hypothesis that damage to the right inferior parietal lobule determines non-lateralized deficits which may contribute to neglect signs [24].

In the present study, line bisection was more sensitive than target cancellation. Similar results were reported in patients with Alzheimer's disease [25]. Simultagnosia and object recognition deficits, which may add noise to patients' performance on visual search tasks, can account for this finding. However, dissociations between line bisection and target cancellation have been previously reported in patients with focal lesions [26], and suggest that partially distinct neurocognitive systems are at work. For example, biased line bisection, which depends on dysfunction of the parietal lobe and of its connections with frontal regions [27], resulted from more posterior brain damage than impaired visual search [26].

The general lack of correlations between neglect severity and the number of years since PCA symptom onset suggests that, rather than a general consequence of late-stage PCA, neglect symptoms occur in certain PCA patients and not in others. Possibly this is because, in some PCA patients, bilateral atrophy can decrease the competitive interactions between the parietal lobes and contribute to lateralized neglect signs.

Diagnosis of neglect has important implications for patient management, because of its dramatic clinical consequences on patients' everyday life[16]. For example, the presence of even mild degrees of neglect or visual extinction puts patients at risk of car accidents if they continue driving. Neglect also increases the risk of falls [28] and may contribute to spatial disorientation and wandering in patients with neurodegenerative conditions. Clinicians should consider the routine use of neglect tests such as line bisection and target cancellation as a cost-effective procedure to screen neurodegenerative patients [29].