Chapter 22 Cortical blindness and visual anosognosia

Chapter 22 Cortical blindness and visual anosognosia

Disorders of Visual Processing Handbook of Clinical Neurophysiology, Vol. 5 GG Celesia (Ed.) © 2005 Elsevier B.V. All rights reserved. 429 CHAPTER 2...

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Disorders of Visual Processing Handbook of Clinical Neurophysiology, Vol. 5 GG Celesia (Ed.) © 2005 Elsevier B.V. All rights reserved.

429

CHAPTER 22

Cortical blindness and visual anosognosia Gastone G. Celesiaa and Mitchell G. Brigellb,* a Neurology Department, Loyola University of Chicago, Stritch School of Medicine, Chicago, IL, USA Clinical Technology, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA

b

22.1. Introduction In this chapter we will discuss some perception disorders including the most severe acquired disorder of perception: cortical blindness. The cortically blind patient may be unable to perceive any visual stimulus or only have preserved rudimentary vision of light and shadows. Yet, some of these patients will deny their blindness and claim to be able to see (Anton’s syndrome or visual anosognosia). Anosognosia of the visual deficit is also seen in hemianopic subjects (hemianopic anosognosia). In the current scheme of visual processing (see Chs 2, 3 and 17), cortical blindness is predicted when both primary visual cortices are disabled either because they are destroyed or because they are disconnected from the extrastriate visual areas (Mesulam, 2000). Less clear is why some patients are unaware of their visual deficit. These issues are complex and relate to the difficult problem of brain and mind. To quote Zeki (1992), ‘The study of the visual system is a profoundly philosophical enterprise; it entails an inquiry into how the brain acquires knowledge of the external word, which is no simple matter.’

fulfills the following clinical criteria: (1) loss of all visual sensations including all, or mostly all, appreciation of light and dark; (2) loss of lid closure to threatening gestures; (3) retention of pupillary reflexes to light and near; (4) normal retinas to funduscopic examination; and (5) retention of full extraocular movements. Bilateral hemianopia is defined as a loss of vision involving the nasal and temporal hemifield of both eyes with sparing of all or part of the central vision due to verified lesions of both occipital lobes (Celesia et al., 1991). Residual rudimentary vision is defined as the ability to perceive changes in illumination and the ability to localize moving targets. The subject, however, is unable to identify the nature of the target and cannot recognize objects or forms. Blindsight is the ability of a patient to respond to a visual stimulus despite the patient being unaware of its presence. Riddoch’s phenomenon is defined as the ability to perceive small moving objects in the affected blind hemifield. The patient is aware of what he sees and has some ability to recognize the moving target (Riddoch, 1917).

22.2. Cortical blindness 22.2.1. Definitions The various deficits related to cortical blindness are defined with current accepted taxonomy. Cortical blindness is defined according the criteria of Celesia et al. (1991). The cortically blind patient

* Corresponding author. Correspondence: 3016 Heritage Oak Lane, Oak Brook, IL 60523, USA; Tel.: (630) 9682199; Fax: (630) 968-2179; E-mail: [email protected]

22.2.2. Etiology Any destructive lesion affecting both occipital lobes may cause cortical blindness (Aldrich et al., 1987; Celesia et al., 1991). The most frequent etiology is a stroke, and specifically occlusion of the tip of the basilar artery causing ischemic infarctions of both occipital cortices. Other etiologies are trauma, cerebral anoxia (drowning, cardiac arrest, carbon monoxide poisoning, eclampsia, etc.), neoplastic invasion of the occipital lobes and CNS infections (Drymalski, 1980; Aldrich et al., 1987; Lambert et al., 1987;

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Celesia et al., 1991; Apollon, 2000; Williams, 2002). Relatively frequent causes of cortical blindness are cardiac surgery and cerebral angiography (Drymalski, 1980; Aldrich et al., 1987; Williams, 2002). The occipital cortex is particularly susceptible to anoxia. Anoxia/hypoxia produces cortical laminar necrosis most prominent in the third and fourth layer of the neocortex, and a selective regional vulnerability with predilection for the visual, premotor and parietal areas (Courville, 1953; Malamud, 1963). Among the visual areas, area 17 is more resistant that the extrastriate areas (Malamud, 1963). Cortical blindness can be transient or permanent depending on the nature of the insult. The devastating effects of permanent blindness are self-evident making the issues of prognosis, treatment and prevention a health priority. 22.2.3. Prognosis 22.2.3.1. Neuroimaging Aldrich et al. (1987) report that, in their series of 25 cortically blind patients, a CT scan (CT) performed at least 1 week after the onset of blindness was a useful prognostic indicator. In all patients with bilateral occipital abnormalities in their CT, vision did not recover. Similarly, in cortical blindness due to cardiac

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surgery or cerebral angiography, if no bilateral infarcts of the occipital lobes are evident, the blindness is transient with partial or total recovery of vision (Lambert et al., 1987; Cristophe et al., 2002; Williams, 2002). In 30 infants and children with cortical blindness, Lambert et al. (1987) reported that the recovery differed significantly with respect to the age at which the hypoxic insult occurred and the extent of neuroimaging abnormalities. Normal CTs or MRIs were associated with good visual recovery, while lesions involving optic radiations were correlated with poor visual recovery. Hypoxic insults occurring at an early age had a worse outcome than a similar insult in later age (Lambert et al., 1987). Cappellini et al. (2002) have applied magnetic resonance spectroscopy (MRS) to evaluate short- and long-term outcome in acute hypoxic encephalopathy in the fullterm newborn. They reported that high lactate levels and low Nacetylaspartate (NAA) were found in the newborn with the worst outcome. Newborns with good outcome had good lactate and NAA levels on MRS. Pu et al. (2000) and Malik et al. (2002) confirmed the value of MRS and focused on increased peaks of glutamate/glutamine as indicators of neuronal injury. As shown in Fig. 22.1, MRS can also be used in adults. Patient BK is a 41-year-old woman who had a cardiac

Fig. 22.1. MRI of patient BK 10 days after cardiac arrest. Note the extensive hyperdense gyral lesions in both occipital cortex and in the left frontal region. The patient at this time was totally blind.

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Fig. 22.2. MRI spectroscopy of the same patient as Fig. 22.1, done 11 days after cardiac arrest. The area sampled is shown on the right. On the left is the spectrum of the gray matter. The patient was blind at the time of the spectroscopy. A normal spectrum suggested a good prognosis.

arrest while shopping. Paramedics resuscitated and intubated her within 2–5 minutes of her arrest. The patient was extubated and appeared neurologically well 3 days after the cardiac arrest. However, in the next 24 hours she became blind and severely ataxic. Five days after the event, the patient was totally blind, unable even to perceive light and darkness. She had normal pupillary responses, normal oculomotor movements and absence of eye blink to visual threat. She was also very ataxic with severe intention tremor. As shown in Fig. 22.2, MRI showed extensive gyral enhancement of the occipital cortex, suggesting laminar necrosis of the third to fourth cortical layers. MRS of the occipital cortex (Fig. 22.1), however, demonstrated normal values of NAA and lactate as well as normal lipid and lactate ratios and normal NAA to creatine ratio (1.58), raising the possibility of substantial visual recovery. During the following 4 months the patient gradually recovered. Her vision returned to a visual acuity of 20/50 in each eye; she had normal color vision, but she was left with a homonymous left inferior quadrantanopia (see Fig. 22.3). The intention tremor and ataxia had subsided and she had a normal gait. It may be concluded that MRI and MRS are good tools to assess the severity of the damage to the visual cortex in cerebral anoxia and cortical blindness. Per-

OS

OD

Fig. 22.3. Humphrey visual fields of patient BK, 4 months after cardiac arrest. The patient had recovered most of her vision. Note the left homonymous lower quadrantanopia.

sistence of abnormal MRI images and/or MRS spectroscopy 10 days or more after an anoxic insult suggests a poor prognosis for substantial visual recovery. These data have been validated both in adults and children. 22.2.3.2. Visual evoked potentials (VEPs) VEPs have been studied in cortical blindness and have not been proven to be of value in the diagnosis or prognosis of blindness. Frank and Torres (1979) recorded VEPs to flashes in 30 cortically blind patients and found no correlation with the prognosis

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for visual recovery. Spehlmann et al. (1977), BodisWollner et al. (1977) and Celesia and Brigell (1999) have recorded preserved VEPs to flashes and pattern stimuli in a majority patients with cortical blindness. The logical question that arises from these data is where VEPs originate from if the visual cortex is destroyed? Closely related is the question of the source of residual vision and blindsight. 22.3. Residual vision, blindsight and VEPs There are two possible explanations for the preservation of residual vision after bilateral destruction of area 17: (1) The information is processed via non-geniculate-calcarine pathways; (2) there are preserved islands of area 17 that still have residual partial function. To address these issues we studied 14 cases of cortical blindness accumulated in the last 30 years of clinical practice by the senior author (GGC). CT scans were done in every subject and MRI in four patients. As shown in Fig. 22.4, there was some variation in the extent of the ischemic lesions in each patient. Patients with total blindness had extensive ischemic infarcts of both striate and adjacent extrastriate areas and extend-

ing to the white matter and optic radiations. Residual vision was associated with small spared islands of area 17 and parastriate cortices (areas 18, 19). Patients with bilateral hemianopia had the most variable lesions with considerable sparing of area 17 and little damage of surrounding areas 18, 19 and the optic radiations. In Table 22.1 we correlate VEP results with the nature of the visual deficit. When the blindness was total, VEPs were absent to large and medium size checks 67% of time and were absent 100% of the time when tested with small 15¢ checks, whereas in patients with residual visual function VEPs were absent 50% of the time to checks of 31¢ and 75% of the time to checks of 15¢. Absent VEPs were observed in only 25% of the time in patients with bilateral hemianopia. As shown in Fig. 22.5, VEPs to pattern stimulation have a normal morphology although they often have a delayed latency. VEP mapping and amplitude distribution was studied in two patients with residual vision (Fig. 22.6) and was found to be within normal limits. To determine the nature of residual vision and the source of VEPs we studied six patients with both VEPs and PET or SPECT. As shown in Fig. 22.7, dipole source localization of flash VEPs shows that

Table 22.1 Correlation of VEPs and severity of cortical blindness. Cortical blindness (absolute)

PVEPs 15¢ Tested Normal Absent Delayed PVEPs 31¢ Tested Normal Absent Delayed PVEPs 60¢ Tested Normal Absent Delayed

Cortical blindness with residual

Bilateral hemianopia vision

Total

N

%

N

%

N

%

N

%

3 0 3 0

100 0 100 0

4 0 3 1

100 0 75 25

2 0 1 1

100 0 50 50

9 0 7 2

100 0 78 22

3 1 2 0

100 33 67 0

4 0 2 2

100 0 50 50

4 2 1 1

100 50 25 25

11 3 5 3

100 27 46 27

3 1 2 0

100 33 67 0

1 1 0 0

100 100 0 0

1 0 1 0

100 0 100 0

5 2 3 0

100 40 60 0

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Fig. 22.4. Composite drawings representing the patients’ lesions observed with CTs or MRIs. Black areas represent lesions observed in all patients. Dashed lines indicate lesions observed in four cases, while dotted areas indicate lesions limited to one patient. Note that the extent of the lesions is greater in patients with total blindness, intermediate in cortically blind patients with residual vision and least in patients with bilateral hemianopia. The right side of the brain is shown on the right side of the template.

the source of the potentials is located both in areas 17 and 18 and that both regions are activated by visual stimulation as measured by SPECT. FDG-PET scanning demonstrated glucose utalization in area 17 in one patient with residual vision. Regional cerebral blood flow and regional glucose cerebral metabolic rate showed activation of areas 17 and 18, 19 during visual pattern stimulation (Fig. 22.8), indicating that residual vision was due to a spared island of striate cortex (Celesia et al., 1982). Of the six patients

studied, two were totally blind. They had profound depression of rCBF in both occipital cortices and had no recordable VEP to pattern stimulation. The other four patients with residual visual function had islands of preserved rCBF in area 17, and recordable pattern VEPs. The evidence from these data indicates that: 1. There is a correlation between the amount of spared striate and extrastriate cortices and useful

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Bilateral Hemianopia

Cortical Blindness Case 1 was totally blind with no residual vision Case 7 and 9 had some residual vision

Binocular stimulation Checks of 31’ Recording from MO Monocular stimulation Check 31’

Fig. 22.5. Representative VEPs in bilateral hemianopia and cortical blindness. The left half of the figure shows the Goldmann visual fields and visual evoked potentials of a 61-year-old man with bilateral hemianopia. On the right half of the figure are VEPs of three cases of cortical blindness.

P143

Case 7 P121.5

Case 9 P99

Case 1

vision. As we stated (Celesia et al., 1991): ‘The amount of tissue that remains intact in the occipital areas determines the quality of preserved vision, from rudimentary vision to a 20/20 visual acuity and macular sparing.’ 2. Rudimentary vision in adult humans is due to spared islands of striate cortex activated via the classic geniculo-striate pathways. 3. Adult humans with bilateral occipital lesions are ‘quite blind despite a preserved tectal system’ (Daroff, 1972). Blindsight is a more complex problem and is discussed in Chapter 23. The preservation of VEPs in our cases suggests that the responses originate in remnants of area 17. This is confirmed by our findings of the dipole source localization and the brain mapping of the VEPs amplitude distribution. Galambos et al. (1967) had shown that lesions sparing only 3% of the optic tract of animals was sufficient to produce normal VEPs. Meredith and Celesia (1982) estimated that only 7 mm of striate cortex is needed to evoke a normal visual evoked response. An important observation in our series, as well as others (Bodis-Wollner et al., 1977; Spehlmann et al., 1977; Frank and Torres, 1979), is the dissociation between visual perception and VEPs. VEPs are electrical responses to a visual stimulus and their presence does not imply conscious perception of visual stimuli.

22.4. Visual anosognosia Anosognosia (from the Greek a, privative, nosos, ‘disease’ and gnosis, ‘knowledge’) refers to unawareness of the presence of disease or body defect. Babinski described anosognosia in 1914 in relation to unawareness of hemiplegia (Babinski, 1914). Unawareness of visual deficits is seen in cortical blindness and hemianopia.

22.4.1. Anton’s syndrome Cortically blind individuals often deny their blindness, as initially described by Anton in 1899. Anosognosia or unawareness of blindness has also been reported in other causes of blindness such as cataracts, optic atrophy and retinopathies (Lessel, 1975). Classically, however, Anton’s syndrome refers to unawareness of cortical blindness. Six (43%) of our 14 cortically blind individuals had Anton’s syndrome. There was no correlation between the extent of visual loss or the severity of occipital lobe lesions and unawareness of blindness. We observed Anton’s syndrome both in patients who were totally blind and in patients with some residual vision. There are several hypotheses regarding the physiopathology of this unawareness of deficit (Anton, 1899; Weinstein and Kahn, 1955; Lessell, 1975; Fisher, 1989; Heilman, 1991; Celesia et al.,

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KC age 65 Pattern reversal 31’ checks

0

Fig. 22.6. Brain mapping of pattern VEPs to stimulation with checks of 31¢. The patient is a 65-year-old man with cortical blindness and residual vision limited to perception of light and darkness. The amplitude maps of P108 and P144 are shown in the right half of the figure.

1997): (1) generalized deterioration of intellectual and cognitive abilities; (2) denial and confabulation with or without deficit in coping mechanisms; (3) release phenomenon; (4) functional and/or anatomical disconnection. Impairment of cognitive functions is occasionally observed in cortical blindness, but we have observed several patients with Anton’s syndrome who had no impairment in memory, language skills and visual imagery. This dissociation suggests that dementia is not the cause of unawareness of blindness. Heilman (1991) noted that some patients with cortical blindness have preserved visual imagery. He suggests that the syndrome is due to a release phenomenon: ‘Normally, visual input inhibits or takes priority over imagery; however, with damage to the visual input system the imagery system is released and provides the speech area with “false” information, leading both to hallucinations and anosognosia’ (Heilman, 1991). Goldenberg et al. (1995) report a

case of Anton’s syndrome with preserved visual imagery and some spared islands of visual cortex. They postulate that this spared cortex generates visual images that are then misinterpreted as real because of lack of inhibitory influences from extrastriate areas. Breier et al. (1995) studied the effect of left-hemisphere anesthesia during the Wada test and reported that anosognosia for hemiplegia was dissociated from anosognosia for hemisensory loss. They concluded that this dissociation would argue against theories of psychological mechanisms or cognitive deterioration. Correlation between the various anosognosias and neuroimaging shows that in each specific anosognosia the lesion is limited to the primary and secondary areas involved in the deficient modality. This, and the dissociation of the various anosognosias, suggests that each sensory system has its own modular organization including its own ‘awareness module’ (Cooney and Gazzaniga, 2003), or what Zeki and Bartels (1999) call ‘its own microconsciousness’. In the cortically

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JB age 81 Flash Stimulation 1 Hz

Fig. 22.7. SPECT and VEPs to flashes in patient JB. The left images represent SPECT cerebral perfusion. Please note that there is decreased perfusion bilaterally in occipital and parietal regions. Photic stimulation induced a 25% increase in perfusion over the occipital areas. On the right of the illustration is shown the dipole source localization of VEPs. Three dipoles were identified, the first represents the electroretinogram to stimulation of the right eye, while the two other dipoles are localized in the striate-peristriate areas. Note that the dipole localization corresponds to the area activated by SPECT.

blind individual, V1 becomes disconnected from higher cortical centers, including the areas mediating visual awareness. Thus, the patient needs to discover the deficit via non-visual channels. 22.4.2. Hemianopic anosognosia Hemianopic anosognosia (HAN) is defined as the unawareness of visual loss in the homonymous hemifield. In a prospective study of 32 consecutive patients with homonymous hemianopia due to ischemic infarct we found hemianopic anosognosia in 20 (62%) patients (Celesia et al., 1997). Gassel and Williams

(1963) reported a similar high frequency of HAN in 31 of 35 patients (85%), while Warrington (1962) reported HAN in 55% of 20 hemianopic patients. 22.4.2.1. Anatomic correlations of HAN HAN occurs in patients with a variety of lesions, with frequent involvement of the territory vascularized by the middle cerebral artery. However, HAN was also observed in patients with small lesions located exclusively in the occipital lobe and limited to area 17 and part of area 18. In these later mentioned patients, the only neurological deficit was hemianopia (pure hemianopia). In Fig. 22.9 we show the lesions of eight patients with pure hemianopia.

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Resting (a)

AG

Visual Stimulation (b)

a-b

Checks 60’ OU

OD

OS

250 msec Fig. 22.8. Regional cerebral blood flow (rCBF) measurements of the left occipital lobe, PET images and VEPs in a 59-yearold male with bilateral occipital lobes ischemic infarcts. The patient perceived light and motion in the right homonymous lower quadrants. rCBF data are shown in the left portion of the illustration. Note the increased rCBF, indicating neuronal activation of striate and extrastriate areas with visual stimulation. The upper half of the right side of the figure shows the PET images in the same patient. The resting state indicates PET with eye open but no visual stimulation. Visual stimulation consisted of flashes presented every 600 msec. The last image to the right indicates the subtraction of a - b and represents the area activated by the stimuli. Pattern reverse stimulation at the same frequency of 600 msec produced similar pictures and is shown in the left histograms as hatched bars. Black bars indicates flash stimulation while the baseline is indicated by white bars. Activation of the spared cortex increased rCBF by 60%. The lower part of the right side of the illustration represents VEPs to pattern stimulation with 31¢ check recorded from the mid-occipital scalp.

These eight patients had normal memory, cognitive, somatosensory and motor functions. Five patients were aware of their deficit while three were not. The lesions in these patients were similar and in none of them was the parietal lobe involved. These data do not support the view (Koehler et al., 1986) that the parietal lobe is responsible for anosognosia. In our sample, lesions limited to V1, V2 and portion of V3, or their connections from the lateral geniculate nucleus (one of the patients with HAN had a lacunar

infarct involving the right retrolenticular portion of the internal capsule, involving therefore the geniculocalcarine fibers), were sufficient to produce HAN. HAN occurred in 16 of 26 patients (62%) with right side lesions but also in four of six patients (67%) with left side lesions. There was no statistically significant difference between right and left side lesions in our sample. This lack of laterality occurred in spite of the sample bias for right side lesions. We excluded patients with large lesions in the territory of the left

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Fig. 22.9. Composite brain section templates representing the patients’ lesions observed with MRI or CT in patients with homonymous hemianopia and without any other neurologic deficits (here labeled pure hemianopia). The right side of the brain is shown on the left side of the template. The gray shaded areas represent lesions of patients with hemianopic anosognosia; thinner outlines represent lesions in patients with pure hemianopia without anosognosia. Modified from Celesia et al., 1997.

middle cerebral artery due to their language disturbances. When we limited the analysis to patients with pure hemianopia, HAN was present in two of five patients with right and in one of three patients with left occipital lesions. Similarly, Breier et al. (1995) demonstrated anosognosia for hemiplegia in 49% of 18 patients undergoing left hemisphere anesthesia. They concluded that anosognosia is underreported in left side brain lesions because of concomitant aphasia. Two major conclusions can be derived by these data: (1) anosognosia can be observed both in right and left side lesions; (2) parietal lobe lesions are neither necessary nor sufficient to explain visual anosognosia. 22.4.2.2. Pathophysiology of HAN The same theories discussed for Anton’s syndrome have been proposed to explain HAN. We will not repeat the discussion but we will focus on the theory of ‘discovery’ (Gassel and Williams, 1963; Levine, 1990; Celesia et al., 1997). The theory is based on the concept that awareness of the deficit requires its discovery. Thus it is logical to expect that factors focusing the attention of the patient on the problem will result in early awareness of the deficit. Patients with positive spontaneous visual phenomena in our series

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were usually (75%) aware of their hemianopia (Celesia et al., 1997). The presence of visual hallucinations or other visual phenomena in one hemifield ‘forces’ the patient to become aware of the problem and hence to discover the deficit. Patients with hemianopic anosognosia will report that the boundaries of the visual field appear normal, therefore they do not perceive any visual loss; very much as normal people do not perceive what is behind their heads although they know something exists. In support of this hypothesis is the transient nature of most HAN and the fact that most patients can become aware of the deficit once it is pointed out to them. However, this explanation cannot be universally applied because it fails to explain some patients with persistent anosognosia. One of our patients had persistent HAN for the last 18 months of follow-up, in spite of specific training on reality testing of the visual deficit. In these cases there may be a failure to activate ‘essential nodes’ necessary for awareness (Crick and Koch, 2003). In this distributed networks of modules, the lesion causing the hemianopia also disconnects V1 from yet to be defined higher-level centers. As was pointed out in Chapter 3 by VanRullen and Koch: ‘the locus of visual awareness is still an open question subject of intense debate’. Visual awareness requires the integration of information distributed in relatively large cortical regions with multiple parallel processes (Maunsell, 1995). Studies of visual perception and imagery with PET showed the activation of area 17, the cuneus, fusiform, lingual, inferior temporal, occipital and angular gyri and the posterior-superior part of the parietal lobe (Roland and Gulyas, 1995). In summary, awareness of the visual deficit requires activation of visual attention and visual awareness centers. Although there is agreement that each sensory system may have his own microawareness modules (Zeki and Bartels, 1999; Cooney and Gazzaniga, 2003), where these ‘centers’ are located or whether they are ‘nodes’ in a distributed network remains to be determined. No single theory can explain HAN because of the complexity of ‘awareness’. HAN may be due ‘at times, to failure of discovery, to hemineglect, to generalized cognitive impairment, to a “filling in” process, or to a combination of these factors’ (Celesia et al., 1997; Stoerig et al., 2002). Fundamental to all these cases is either a destruction or disconnection of visual cortices from higher cortical centers and a disruption of a complex distributed network.

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