Cortical blindness is the loss of vision and visual fields due to damage to the bilateral occipital visual cortex (primary visual cortex). The eyes themselves are normal, and pupillary reflexes and fundoscopic findings are characteristically normal.
Anton Syndrome is a state of visual anosognosia in which patients with cortical blindness are unaware of their vision loss and describe nonexistent visual experiences. Despite being blind, patients engage in confabulation, attempting to describe what they see in detail.
This disease is named after the Austrian neurologist Gabriel Anton. Anton reported a 69-year-old case with bilateral temporal lobe lesions presenting with acquired anosognosia and hearing loss. The term “anosognosia” was coined by Joseph Babinski, so it is also called “Anton-Babinski syndrome.” The first description of visual anosognosia dates back to the Roman slave Harpaste, who denied her blindness and complained that the room was dark.
Unilateral occipital to parietal lobe lesions may not lead to cortical blindness but can present with hemispatial neglect.
Difference from Charles Bonnet syndrome requires attention. Charles Bonnet syndrome involves visual hallucinations in patients with visual impairment, but insight into their visual impairment is preserved, fundamentally differing from Anton syndrome.
Epidemiology: The median age is 55 years (range 6–96 years), with no sex difference. The most common cause is secondary to cerebrovascular accident (CVA), often in elderly patients with multiple vascular risk factors. Posterior cerebral artery (PCA) stroke accounts for 5–10% of all strokes. 1) Between 1965 and 2016, only 28 cases of Anton-Babinski syndrome were reported, making it an extremely rare disease. 2)
Anton syndrome is a condition in which patients with cortical blindness deny their own blindness and confabulate, lacking insight. In contrast, Charles Bonnet syndrome involves visual hallucinations in visually impaired patients, but they retain insight into their visual impairment. Both conditions involve visual impairment, but they fundamentally differ in the presence or absence of anosognosia.
The afferent pathway of the light reflex diverges to the pretectal area of the midbrain before the lateral geniculate body (LGB) and does not pass through the occipital lobe (primary visual cortex). Therefore, even if the occipital lobe is damaged, the light reflex is preserved. Together with normal fundus findings, this is a characteristic finding of cortical blindness.
The main causes and related risk factors for cortical blindness and Anton syndrome are shown below.
Vascular Causes
Bilateral PCA infarction: The most common cause. Infarction of both posterior cerebral arteries leads to extensive damage to the occipital lobes.
Post-trauma/tumor: May occur after head trauma, brain tumor, or surgery.
Cardiac surgery/cerebral angiography: Known iatrogenic risk factors.
Carbon monoxide poisoning / PRES: Can also occur in toxic and reversible posterior leukoencephalopathy syndrome (PRES). Anticancer drugs such as cisplatin are also causes.
Non-vascular causes
MELAS: Mitochondrial encephalomyopathy. Onset has been reported in cases with mt.3243A>G mutation. 2)
MS exacerbation / hypertensive encephalopathy of pregnancy / obstetric hemorrhage: Secondary to various systemic conditions.
Infectious diseases: West Nile virus (WNV) encephalitis, HIV-related PML, etc. 3)
Others: Adrenoleukodystrophy, central nervous system vasculitis, ischemia associated with subarachnoid hemorrhage, bilateral optic radiation lesions in Trousseau syndrome, etc.
An anatomical feature of the posterior cerebral artery (PCA) is that it branches from the basilar artery, supplying deep structures (posterior thalamus and midbrain) in its proximal segment (P1–P2) and the occipital cortex in its distal segment (P3–P4). Damage to the P4 segment is the main cause of visual field defects. 1) The occipital cortex is distant from the central vascular system and has a structure vulnerable to ischemia.
It can also develop from various non-vascular causes such as MELAS (mitochondrial encephalomyopathy) 2), MS (multiple sclerosis), West Nile virus encephalitis 3), trauma, and carbon monoxide poisoning. In all cases, bilateral occipital lobe dysfunction is the common pathological basis.
Clinical diagnosis is made by combining four elements: history of confabulation, clinical evidence of vision loss, normal fundus findings, and imaging confirmation of occipital lobe damage.
The diseases to be differentiated and the key points for differentiation are shown below.
| Disease | Key differentiating points |
|---|---|
| Charles Bonnet syndrome | Visual hallucinations present, insight preserved (no anosognosia) |
| Dementia | Cognitive anosognosia, confabulation due to memory impairment |
| Wernicke-Korsakoff syndrome | Thiamine deficiency, immediate memory preserved |
| Malingering | VEP demonstrates normal central visual function |
| Psychogenic visual disturbance | No abnormalities in eye or pupillary light reflex (common with cortical blindness); psychiatric evaluation needed |
| PRES (Posterior Reversible Encephalopathy Syndrome) | MRI shows reversible edema in posterior white matter; improves with blood pressure management |
Differentiation from psychogenic visual disturbance is particularly important. Cortical blindness due to bilateral occipital lobe injury shows no abnormal findings in the eye and the pupillary light reflex is preserved, so it is easily mistaken for psychiatric disease or malingering.
Treatment for Anton syndrome is selected based on the presumed cause of occipital lobe damage. Causal treatment is fundamental.
Antiplatelet Drugs
Aspirin: 75–150 mg/day (Grade A)
Clopidogrel: 75 mg/day (Grade A)
Cilostazol: 200 mg/day (Grade B)
Ticlopidine: 200 mg/day (Grade B)
Other Preventive Treatments
Anticoagulants: Warfarin, etc. Indicated when caused by cardioembolism (e.g., atrial fibrillation).
Statin therapy: Management of dyslipidemia and prevention of stroke recurrence.
Risk factor management: Normalization of hypertension, hyperglycemia, and dyslipidemia; smoking cessation.
After acute treatment, rehabilitation including visual compensatory training is important. This involves utilizing residual visual pathways (such as blindsight) and training compensatory strategies using other senses (auditory, tactile).
If the cause is reversible (PRES, hypotension, transient blood flow disturbance), partial recovery can be expected, but visual recovery is difficult in cases of extensive infarction. Young age and absence of underlying disease are considered good prognostic factors.
In cases of stroke origin, tPA (thrombolytic therapy) is indicated within 4.5 hours of onset. 1) Beyond this time, prevention of recurrence and rehabilitation become the mainstays of treatment. The more time available, the greater the extent of salvageable neurons, so it is important to seek emergency care immediately upon symptom onset.
Bilateral extensive damage to the occipital lobes (primary visual cortex V1) leads to bilateral homonymous hemianopia and eventually cortical blindness. The occipital cortex is distant from the central vascular system and is vulnerable to ischemia. Infarction of the distal posterior cerebral artery (P3–P4) disrupts blood flow to the occipital lobes. 1)
Visual information processing involves the ventral stream (“what” pathway: V4 area, form and color recognition) and the dorsal stream (“where” pathway: V5 area, spatial location and motion recognition). Some subcortical fibers bypass V1 and directly connect to V4 and V5, so even when V1 is extensively damaged, these pathways may function, allowing color perception and motion detection. 1) This is the neurological basis of Riddoch phenomenon (seeing moving objects).
As for the mechanism of blindsight, studies using macaque monkeys have reported direct projection pathways from LGBd to V2, V3, V4, V5/MT, FST, and LIP, which may explain unconscious visual responses.
Several hypotheses exist regarding the mechanism of anosognosia.
| Hypothesis | Content | Evidence |
|---|---|---|
| Simultaneous damage to visual cortex and association cortex | Primary visual cortex and visual association cortex are simultaneously impaired, leading to lack of insight into one’s own condition | Clinical picture of extensive occipital lobe lesions |
| Disconnection syndrome | Parietal white matter lesions disconnect the visual cortex from other areas | Occurs in cases with white matter lesions |
| Abnormal connection with language centers | The connection between the damaged visual cortex and the functioning language area is severed, causing the language area to generate confabulatory responses without visual input | Confabulation content includes visual details |
Currently, the “abnormal connection with language centers” theory is the most supported. It is thought that when feedback from the damaged visual cortex to the language area is interrupted, the language area generates false reports of “seeing.”
The most supported hypothesis is the “disconnection from language centers” theory. Damage to the occipital lobe disrupts the feedback circuit from the visual cortex to the language area, causing the language area to generate confabulatory responses of “seeing” without visual input. This is not intentional lying but a neurological phenomenon resulting from brain circuit damage.
Mechanism in MELAS: Abnormal mitochondria accumulate in the endothelial and smooth muscle cells of small arterioles, leading to capillary proliferation. Seizures cause rapid energy depletion in the neurovascular unit, resulting in a Todd paralysis-like condition. The Fryer hypothesis proposes that “seizures trigger stroke-like episodes.” 2)
Mechanism of blood-brain barrier (BBB) crossing in WNV encephalitis: Three pathways are hypothesized: passive cellular transport, axonal transport, and inflammation-induced BBB disruption. 3)
A case report by Ziaul et al. (2024) reported that COVID-19 patients have a 3.6-fold increased risk of ischemic stroke, and even mild COVID-19 increases stroke risk to about 1%. 1) High inflammatory response, hypercoagulable state, and medical severity are considered predisposing factors for thromboembolism. Delayed medical consultation during the pandemic was also a problem for strokes in the posterior circulation, including PCA.
Ewida et al. (2021) reported a case of Anton-Babinski syndrome complicated by MELAS, with characteristic MRI findings of DWI hyperintensity and ADC isointensity (inconsistent with ischemic changes). 2) This finding differs from DWI changes in ischemic stroke (with ADC reduction) and is interpreted as a combination of reversible energy metabolism impairment and hemodynamic changes due to epileptic seizures. Differentiation of DWI findings provides important implications for treatment decisions in MELAS.
Srichawla (2022) reported that interferon alpha and purified immunoglobulin preparations containing WNV antibodies may be future treatment candidates for neuroinvasive WNV infection. 3) Currently, response to existing drugs including methylprednisolone is poor, and no established treatment exists. Over 80% of WNV infections are asymptomatic, but less than 5% progress to neuroinvasive disease, making the establishment of treatment urgent.
