Charles Bonnet Syndrome
Charles Bonnet Syndrome (CBS), named after the Swiss scientist who first described visual hallucinations in his grandfather in the 1970s, has three features: hallucinations, ocular pathology, and intact cognition.
CBS most commonly occurs in elderly individuals who have a severe visual impairment commonly due to age-related macular degeneration. Other ocular impairments causing CBS include retinitis pigmentosa, severe myopia, glaucoma, cataract, diabetic retinopathy, and optic neuritis . CBS has also been found in patients with vascular associated vision loss including central retinal artery occlusion, retinal vein occlusion, temporal arteritis, and occipital infarction. Ocular procedures have also been noted to induce CBS, including CE/PCIOL, bilateral laser iridotomies, anti-VEGF injections, and enucleation.
Although CBS is mostly seen in the elderly, it can occur among children in the setting of visual pathology. Irrespective of age of onset, CBS occurs with sudden and unexpected vision loss and has not been found to occur in lifetime visual blindness.
Several risk factors for CBS have been noted with some degree of inconsistency. The most commonly accepted risk factors include worsening visual acuity and older age. Other proposed risk factors include social isolation, cortical atrophy, and cognitive impairment. Additionally, while there is no consensus on whether men or women are more commonly affected, some studies have observed that women are commonly affected.
CBS is believed to be underrepresented due to under-reporting of visual hallucinations out of fear of being considered mentally unstable, as these patients realize that their hallucinations are not real. Further exacerbating this issue are the absence of specific diagnostic criteria and the lack of awareness of this condition among patients. Taken together, these factors have rendered estimation of the prevalence of CBS difficult to ascertain, ranging from 0.4-39% among individuals with visual impairments.
Content of the visual hallucinations is extremely varied and can be categorized as simple or complex. Simple hallucinations can include flashes of light or patterns; complex hallucinations include images of people, animals, plants, inanimate objects, and life-like scenes and commonly, an individual will experience different hallucinations in each episode. The images may be in color or in black and white; they may be familiar or foreign to the individual experiencing the hallucination. In some cases, the hallucination experienced appear real at first, as the hallucination can seem congruous and plausible with reality in that moment, but some hallucinations appear markedly detached from reality. Some reported personal and emotional meaning to their hallucinations while others did not, and the patient is generally unable to consciously influence their hallucinations. Regardless, all individuals recognize that their hallucinations are not reality.
Patients have reported images lasting for varying amounts of time from seconds to hours. Many triggers have been suggested such as fatigue, stress, and differing levels of light. Resolution of the hallucinations often occurs spontaneously but occurs due to a variety of causes.
The course of CBS varies: some episodes of hallucinations reportedly occur daily, weekly, monthly, as well as only a few episodes per year. Based on their frequency, the hallucinations can be classified as episodic, periodic, or continuous. Episodic hallucinations consist of a single episode of hallucinations occurring over a period of days to months and then resolving permanently. Periodic hallucinations are defined as occurrences of hallucinations followed by hallucination-free periods. Individuals experiencing continuous hallucinations do not experience remission of the hallucinations.
Deficits in any part of the visual pathway can cause CBS, yet the underlying mechanism of the hallucinations is unknown. Several theories have been proposed including phantom limb in the context of vision, reduced sensory input, perceptual release, and deafferentation. The theory of reduced sensory input is underpinned by the idea that dreams and hallucinations exist on the same continuum; reduced sensory input results in a state similar to sleep, causing the brain to create images. Reduced sensory input is somewhat related mechanistically to the theory of perceptual release, which suggests that normally filtered visual information is allowed to enter consciousness as a result of decreased visual input.
The most commonly accepted theory is deafferentation. In this context, deafferentation refers to the loss of afferent neurons responsible for vision transduction. This typically is due to a lesion in the visual pathway, which is always seen in CBS. The loss of the afferent fibers results in aberrant hyperexcitability in the visual cortex and can be attributed to a host of factors, including an increase in presynaptic release of neurotransmitters, an increase in the number of postsynaptic receptors, and a decrease in inhibitory neurotransmitter release; these changes give rise to visual hallucinations. 
There is limited data regarding the effect of CBS on mortality. One study found patients with CBS to have a higher mortality overall when compared to the general population indicating that this may be a marker of mortality however, further investigation is required. The risk of developing dementia has become an emerging issue in the literature; however, data on this matter is inconclusive. One study found that some patients later develop dementia or Lewy body dementia. The development of dementia may be confounded by age, as most patients who are diagnosed with CBS are elderly. Those who develop Lewy body dementia possibly were misdiagnosed with CBS; their symptoms may be attributable instead to early Lewy body dementia.
While CBS may not negatively impact most patients, 33% of patients can experience negative outcomes including distress if they have experienced chronic, frightening hallucinations, stigma due to CBS being misattributed to a mental disorder, and diminished quality of life.
For those with CBS due to correctable eye diseases, the hallucinations may spontaneously remit or improve with the treatment of the underlying cause of visual loss. For example, patients with CBS caused by macular degeneration reported resolution of hallucinations with PDT and patients with cataracts had resolution of CBS with CE/PCIOL.
Most often there is no known treatment for this condition. Management requires awareness by physicians treating patients with visual impairments and primarily consists of providing empathy and reassurance. Some medications have been tried such as antipsychotics, antiepileptics, cholinesterase inhibitors,SSRIs, and levetiracetam showing benefit in individual patients.Pharmacologic therapy may be considered in cases of disturbing hallucinations causing significant distress to the patient. However, non-pharmacologic methods are preferred with eye closure, repeated blinking, appropriate lighting, and reducing patient isolation as possible approaches. Ultimately, it is very important for health care providers to recognize this syndrome and to avoid misdiagnosing a cognitively intact individual as this can lead to unnecessary and potential harmful treatment.
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