Anoxic Brain Injury in Ophthalmology

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Article initiated by:

Amna Ali, Andrew Go Lee, MD, Osama Al Deyabat, MBBS, Saif Aldeen Alryalat, MD

All contributors:

Nagham Al-Zubidi, MD, Osama Al Deyabat, MBBS

Assigned editor:

Osama Al Deyabat, MBBS

Review:

Assigned status Up to Date

 by Osama Al Deyabat, MBBS on October 08, 2024.

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Contributing Editors:	add

Anoxic Brain Injury in Ophthalmology

Disease

Anoxic brain injury (ABI) results from decreased blood flow to the brain tissue, leading to damage or impairment of brain function. Many patients expire without regaining consciousness; however, due to advancements in techniques in resuscitation and artificial life support, an increased number of patients are surviving, albeit with neurologic deficits. Depending on the location and severity of the causative insult, ABI can result in lasting damage to the visual system, including the cranial nerves, optic nerve, chiasm, or tract; the optic radiations (temporal and parietal lobe); or visual cortex (occipital lobe).

Etiology

1.2.1 In pediatrics

In infants, ABI is one of the most common causes of morbidity and mortality. Causes of ABI include complications or traumatic events before (in utero), during, or after birth including cardiovascular or respiratory issues, congenital infections, and genetic factors. The prevalence of ABI among neonates is increasing due to higher survival rates among premature infants. In children, ABI can be caused by dehydration and abusive head trauma.

1.2.2 In adults

In adults, ABI can occur following trauma (such as strangulation or traumatic brain injury), cardiac or respiratory arrest, acute vascular insult,  or toxicity/poisoning (e.g., carbon monoxide or drug overdose).

Pathophysiology

Watershed areas in the brain are vulnerable to ABI, including the cerebral and cerebellar cortex, hippocampus, basal ganglia, parieto-occipital region, and occipital lobe. More specifically, the primary visual cortex receives blood supply from the terminal end of the posterior cerebral artery; under hypotensive conditions, perfusion may be inadequate, leading to ophthalmic symptoms. Another theory explaining isolated occipital lobe damage in ABI is that the granular cells of the primary visual cortex are less resistant to hypoxia.

Without cerebral perfusion, patients experience depletion of oxygen stores and loss of consciousness within a few seconds.  After five minutes, glucose and oxygen stores are depleted, leading to impairment of ATP production and dysfunction of ATP-dependent membrane pumps and secondary ABI. Subsequent loss of cellular membrane integrity leads to an influx of calcium ions and release of glutamate which binds to NMDA receptors. High levels of intracellular calcium contribute to the disruption of the electron transport chain and the formation of free radicals, furthering neuronal cell damage and death.

Epidemiology

It is difficult to quantify the incidence of ABI due to its diverse causes. Among patients who survive cardiac arrest, 50 to 83 percent may experience clinically significant cognitive symptoms. Visual dysfunction following an ABI  is relatively common with cortical visual impairment (in up to 50 to 70 percent), photosensitivity (50 percent),  and oculomotor dysfunction (60 to 85 percent). The extent and location of brain damage following ABI  in turn determines the likelihood of visual symptoms.

Diagnosis

Table 1. Findings of ABI Affecting the Occipital Lobe

Symptoms and Signs	Ophthalmic Exam	Imaging
●      Cortical blindness ●      Blurred vision ●      Decreased peripheral vision ●      Unusual ocular movements ●      Ocular dipping ●      Neurocognitive deficits	●      Homonymous hemianopia or juxtaposed homonymous hemianopia with or without macular sparing ●      Optic atrophy	●      MRI: Subtle, delayed changes in cortex and deep gray matter areas ●      CT: Diffuse edema with effacement of CSF, reversal sign, white cerebellar sign within days of initial insult ●      PET: Hypoperfusion or hypometabolism

Symptoms and Signs

Patients with ABI affecting the occipital lobe may complain of blurred vision,  decreased peripheral vision (homonymous hemianopsia), or cortical blindness in the acute period. Abnormal ocular movements and ocular misalignment may also occur following ABI.

Unusual ocular movements can also occur in ABI. Verma et al. described a patient who experienced  “abnormal spontaneous, high frequency vertical ocular movement in both eyes, equal in amplitude and velocity without inter-saccadic pause,” one day following an exacerbation of respiratory illness.  Jeanneret et al. described ocular dipping after an ABI due to cardiac arrest.

Typically however patients with ABI and visual complaints report concomitant neurocognitive deficits including slow information processing and short-term memory deficits, as well as dizziness, headaches, and behavioral changes. Disorders of attention and consciousness are also commonly reported following ABI.

In the months following the insult, patients may regain some visual function. Patients may also report visual hallucinations following visual loss (Charles Bonnet phenomenon). Hallucinations however may occur during the clinical course of partially recovering visual cortex after ABI. An EEG may be needed to exclude occipital seizures in such cases.

Ophthalmic examination

Ophthalmic manifestations of ABI include deficits in visual acuity, visual field, and oculomotor function. Automated perimetry (e.g., Humphrey visual field) may show homonymous hemianopsia or juxtaposed homonymous hemianopsia with (central island sparing) or without (cortical visual impairment) macular sparing in one or both hemifields. Damage to the superior occipital lobe, may produce an inferior homonymous hemianopic quadrantic visual field defects versus damage to the inferior occipital cortex and secondary superior homonymous hemianopic loss. Parmar et al. documented bilateral juxtaposed homonymous hemianopias or quadrantanopias involving the upper and lower quadrants months after their initial insults. These juxtaposed visual field defects can mimic altitudinal visual field loss or produce unusual checkerboard visual field defects. Margolin et al. shared similar findings in a patient who experienced an episode of cardiogenic hypoxia and hypotension and retained severely constricted visual fields one year afterward.

In ABI alone, patients will not show evidence of any structural issues with the eye but some patients have concomitant optic atrophy from anoxic ischemic optic neuropathy secondary to ABI. Hypoxia induces increased levels of CCAAT-enhancer-protein homologous protein (CHOP), a marker of increased stress on the endoplasmic reticulum, and glial fibrillary acidic protein (GFAP) expression in the retina and optic nerve. This in turn leads to the death of oligodendrocytes.

Diagnostic procedures

Patients with ABI  may have normal or near-normal neuroimaging initially. Over time, magnetic resonance imaging (MRI) may show encephalomalacia or atrophy. Documented abnormalities may include changes in the cortex, specifically in the peri-rolandic and parieto-occipital areas, and deep grey matter, specifically the caudate, putamen, globus pallidus, and thalamus on diffusion-weighted imaging (DWI) and T2-weighted imaging within six days of the original insult. Gray matter structures are often the first to demonstrate ischemic changes on imaging due to higher metabolic oxygen and glucose demands. In one series of nine patients who experienced cortical visual loss following ABI (systemic hypotension or cardiac arrest),   subtle abnormalities in imaging in cortical vision loss were noted over time. Serial  MRI  months later, however, demonstrated significant brain volume loss in the primary visual cortex.

On computed tomography (CT), diffuse edema with effacement of the cerebral spinal fluid containing spaces may be seen, in addition to loss of gray-white matter differentiation. In a small number of patients who experience ABI, CT imaging may demonstrate the reversal sign, which is the reversal of the normal CT attenuation for gray and white matter. This is thought to be caused by distention of the deep medullary cerebral veins secondary to venous outflow obstruction caused by increased intracranial pressure following ABI. An additional finding is the white cerebellum sign, a component of the reversal sign in which there is high attenuation of the cerebellum and brainstem and hypoattenuation and diffuse edema of cerebral hemispheres. Positron emission tomography (PET) scans may show hypoperfusion and hypometabolism even in cases where the structural imaging (CT or MRI) was unremarkable.

Specific findings on electroencephalogram (EEG) may suggest an ABI has occurred, including alpha-theta pattern, intermittent or continuous seizures, burst suppression, generalized periodic complexes, complete or near suppression, and generalized or focal low-voltage output. However, EEG is less frequently used in routine diagnosis of ABI due to the presence of confounding variables such as drug use, metabolic abnormalities, or sepsis.

Management

There is no proven effective therapy for post-ABI-related visual loss. Occupational therapy (OT), physical therapy (PT), and low vision and vision therapy (VT) may be useful in patients experiencing symptoms and signs of ABI including cortical visual loss. Through occupational therapy-related vision rehabilitation, patients learn compensatory techniques and substitution, techniques that may improve function.

Prognosis

Generally, the prognosis of visual recovery following ABI is guarded. Ngankam et al, reported that 83 percent of patients experiencing cortical visual deficits recovered some visual acuity following rehabilitation. The extent of visual recovery following ABI is dependent on several factors, one of the most important being the severity of the initial anatomic insult. Patients who have complete cortical blindness on initial presentation are more likely to have concomitant neurocognitive and behavioral symptoms, as well as worse final functional outcomes compared to those with partial visual deficits on initial presentation. Additional factors that may contribute to recovery include age, clinical phenotype (i.e. if seizures are present), and genetic vulnerability of the individual. Patients without signs of significant structural changes on neuro-imaging demonstrate a higher likelihood of recovery from cortical blindness.

Conclusion

Clinicians should be aware of the afferent and efferent manifestations of ABI. Initial structural neuroimaging (CT and MRI) may be normal or near normal and serial neuroimaging may be necessary to demonstrate atrophy/encephalomalacia over time. Functional imaging studies (e.g., PET scan) may show hypometabolism in such cases. Visual loss in ABI may be due to ischemic optic neuropathy, homonymous hemianopsia, or cortical visual impairment. Ophthalmoplegia, nystagmus, and abnormal ocular movements may occur in patients with brainstem ischemia following ABI. Although there is no cure for ABI, appropriate multidisciplinary rehabilitation may improve final prognosis.