Continuing Education Activity

Charles Bonnet syndrome (CBS) is a phenomenon characterized by complex visual hallucinations in visually challenged patients but otherwise psychologically normal. The phenomenon was first described in 1760 by Swiss philosopher Charles Bonnet who observed this phenomenon in his grandfather, who was visually impaired due to cataracts. In this phenomenon, the hallucinations have been described as formed, vivid, of realistic objects or people, and they tend to recur. In CBS, the patient is aware that the image is not real and may see these images as disturbing. However, hallucinations can also fit in the visual phenomenon and may be indiscernible from real objects. Hallucinations are described as the perception of unrealistic images, sounds, or smells in the absence of any external stimulus. Hallucinations in older people are usually markers of underlying neurological disorders like Alzheimer disease, parkinsonism, delirium, sensory deprivation, insomnia, or psychosis. The other type of hallucination is release hallucination which usually originates from the external world but is experienced when there is an inadequate stimulus to the sensory system. The hallucinations in CBS are visual and complex but are not disturbing. CBS can also be a marker of dementia in elderly patients. CBS can manifest when there is a lesion at any level of the visual system, and typically patients manifest with a loss of central visual acuity. CBS is also associated with ARMD with a secondary decline in visual acuity. This activity deals with the etiology, epidemiology, and pathophysiology of CBS and highlights the role of the interprofessional team in the investigation and treatment of CBS.

Objectives:

• Describe the etiology of Charles Bonnet syndrome.
• Review the epidemiology of Charles Bonnet syndrome.
• Summarize the clinical findings of Charles Bonnet syndrome.
• Explain the treatment of Charles Bonnet syndrome.

Introduction

Charles Bonnet syndrome (CBS) is a medical condition in which complex visual hallucinations occur concurrently with visual changes, specifically visual field loss or visual acuity loss.[1] As the disease occurs in those with visual impairment or vision loss, the pathways leading to CBS include any involvement in the visual pathway, including the optic nerve, brain, or eyes.[2]

Due to the nature of hallucinations and the most common etiologies, CBS often goes unrecognized and misdiagnosed with early dementia or psychosis. The patient is usually unaware of the unreality of visual experiences, which are typically normal to the brain but sometimes may result in distress. The patient has minimal or no control over the hallucinations, which are clear, well-defined, organized images.[3]

The Swiss scientist Charles Bonnet initially described CBS in 1760, who first noticed this phenomenon of visual hallucination in his 90-year-old grandfather, who was suffering from cataracts.[4] The grandfather underwent cataract surgery and the initial vision improved, but later the visual acuity deteriorated, and he noticed visual hallucinations.[5] The hallucinations were unreal, and the grandfather didn't suffer from psychiatric disorders. This is a kind of release phenomenon due to the deafferentation of the cerebral cortex's visual association areas, giving rise to phantom vision.[6]

Cognitive malfunction, social isolation, and sensory deprivation have been liked as the primary etiologies of CBS. CBS is often missed until the elderly age group due to fear of being labeled as mentally retarded and phobia of admitting hallucinations.[7]

Patients who notice the unreal nature of their hallucinations may be depressed by the fear of imminent insanity. A detailed and systemic history is essential to rule out the existence of hallucinations. The hallucinations may improve spontaneously, or on improvement with vision, or dealing with social isolation.[8]

Anticonvulsants have been shown to improve and abort hallucination, but there is no drug of choice for CBS. The awareness of the Ophthalmologist and the physician are the critical components of management.[9]

Pathogenetic Theories of Charles Bonnet Syndrome

• Sensory deprivation—phantom vision
• Dreams and hallucinations
• Theory of perceptual release
• The neuromatrix theory
• Irritative and release hallucinations
• Social isolation
• Senescence
• Psychological factors
• Cerebral perfusion theory[10]

Etiology

Except for congenital blindness, CBS can originate from any factor affecting the visual pathway, extending from the visual cortex down to the eyes.[11]

Common etiologies include

• Diabetic retinopathy
• Age-related macular degeneration
• Cerebral infarctions
• Glaucoma
• Macular degeneration
• Cataract
• High myopia
• Retinitis Pigmentosa
• Optic Neuritis
• Retinal vein occlusion
• Central retinal arterial occlusion
• Occipital stroke
• Temporal arteritis

The proposed theory for CBS is the phantom limb pain theory. Phantom limb pain theory explains a feeling of pain even when the limb has been removed. The patient feels pain even though the limb has been removed. Similarly, patients with CBS may have visual sensations despite being unable to see them.[12]

Epidemiology

The incidence and prevalence of CBS are still under investigation and require further research. However, various studies and surveys indicate that the condition is not as uncommon as one might think. CBS prevalence has been found to differ widely depending on different sample sizes, with estimates ranging from 1% to nearly 10%.[13] 

One large study aimed at investigating CBS found the overall prevalence to be 0.5% (5/1000), with 0.8% (1/120) of their sample being in those with low visual acuity, 0.6% (2/346) being in the elderly, and 0.8% (1/120) being in both the elderly and those with low visual acuity.[13]

Further highlighting the predominance in those with a higher degree of visual impairment or even more in those with complete vision loss, a study comparing visual hallucinations in people with macular disease versus people with glaucoma involved in a visual rehabilitation found the prevalence of CBS to be 39% and 20% respectively.[14]

Regarding age, CBS can affect all ages; however, it tends to be more prevalent in older individuals. Data on CBS shows the mean age of the condition to be 70 to 85 years old, the expected range where pathological processes leading to visual impairment or vision loss naturally occur.[11][15][16]

However, literature has suggested that CBS is vastly under-reported, mainly due to patients fearing being diagnosed with a psychiatric illness.[17][18] For instance, one study found that a significant number of patients are unaware of the disease, with only 12% of patients in a retinal clinic knowing of CBS.[19] In contrast, another study found that visual hallucinations were reported in only 11 to 15% of older individuals with impaired vision.[20]

CBS is more common in elder patients. Previous reports have revealed the mean age of incidence ranging from 74 to 84 years. CBS has also been reported in children having a high incidence of rapid visual loss. The incidence of profound visual loss is also reported more commonly in the elderly. De Morsier noted a male preponderance; some studies showed a female preponderance, while some showed no sex bias.[21]

Pathophysiology

The pathophysiology of CBS first starts with any factor that leads to loss of vision. These factors which can affect any part of the visual pathway commonly include cataracts, glaucoma, diabetic retinopathy, age-related macular degeneration, and cerebral infarction affecting the visual cortex.[17][11][15] 

The current and most commonly accepted theory for the visual hallucinations seen in CBS is that visual sensory deafferentation results in disinhibitions of cortical regions affecting vision.[14][22] 

Ultimately, this disinhibition leads to spontaneous firing of these vision-associated regions, resulting in hallucinations. Studies supporting this theory have shown through neuroimaging that visual cortical regions, such as the ventral occipital lobe, spontaneously fire during hallucinations in patients who met diagnostic criteria.[23] 

Furthermore, neuroimaging also revealed that the hallucinations correlate with the functions of the involved firing cortical region. Due to the process by which the hallucinations are understood, CBS is not seen in congenital blindness.[24]

History and Physical

Patients with CBS will report a history of "release hallucinations," which is often synonymous with CBS, describing visual hallucinations that occur in individuals with vision loss related to the brain, optic nerve, or eye involvement.[25][16][26][27] 

Patients with chronic slow-progressing ocular disease typically report hallucinations at least one year after severe visual impairment or complete vision loss.[17][28][15] In comparison, patients with acute vision loss secondary to the optic nerve or brain damage will typically report hallucinations within hours or days of inciting events; however, hallucinations can still be reported within months as well.[29][30][31][32] 

The visual hallucinations can vary from described events such as light flashes, shapes, or lines to complex events, including formed images and scenes.[33][34] Furthermore, it has been reported that in patients with CBS in which vision loss was attributed to neurologic or retinal causes, simple hallucinations were more prevalent than complex ones at 90% and 37%, respectively.[31] 

Hallucinations are typically colored and range in the visual field from being animated, static, or moving en block. Patients will also report that hallucinations are more prevalent with eyes open than closed. Patients with CBS will also often report distress from their hallucinations, even though they often recognize them as unreal and disconnected from themselves. Lastly, in obtaining a patient's history, it is essential to note that CBS is not associated with sensory or auditory hallucinations.[34] 

Moreover, the hallucinations observed in CBS can be typically simple or complex, even though a full complex spectrum of hallucinations can exist.[18] Simple hallucinations can be elementary or formed and composed of photopsia, a grid-like pattern, simple pattern shapes, or branching patterns.[28]

Complex visual hallucinations are composed of lucid and complicated images of people, faces, animals, plants, flowers, trees, vehicles, and images of objects.[25] Outside of the history of visual hallucinations, physical examination involves assessing any processes of vision loss.[35]

Ophthalmologic examination, identifying features like glaucoma, macular degeneration, cataracts, and retinal or optic nerve damage, can also be critical components of the physical exam as CBS requires visual impairment to be concurrent with reported visual hallucinations.[15] Neurological deficits seen in cerebrovascular accidents can also be seen in presentation as damage to the cortex involving the visual pathway is another crucial component of CBS.[11]

In a study from London, 38% of the 492 subjects reported visual hallucinations as frightening, horrifying, and startling during the onset. With time the emotional inputs to hallucinations reduced to 8%.[17]

In 60% of patients, visual hallucinations didn't affect their lives, 33% said it had a negative impact, and 7% felt it had a good effect on their lives.[11] However, the definition of CBS mentions complex visual hallucinations. In clinical practice, the patients frequently present with simple visual hallucinations.[18]

The patients manifest with some level of visual impairment; the visual hallucinations are better with more clarity than the residual vision. These visual hallucinations are vivid and are not under voluntary control. The hallucinations are exclusively visual and do not involve any other sensory modality. CBS patients manifest hallucinations when awake, alert and conscious. The patients have no dementia, and their mental function is preserved. The mental intellect, awareness, reasoning, judgment, and applications of knowledge are intact.[34]

Evaluation

The first step in evaluating for CBS is assessing for neurocognitive disorders, neurological deficits, and neurocognitive impairment through a comprehensive neurological examination. Workup can include brain imaging, electroencephalography (EEG), laboratory exams, and genetic testing depending on suspected neurological conditions. 

A medication reconciliation assessment for hallucinations induced by medications should also be completed. Some common non-psychotropic medicines that have been found to cause hallucinations include beta-blockers, glucocorticoids, angiotensin-converting enzyme inhibitors, cimetidine, ranitidine, sildenafil, digoxin, carbapenems, penicillins, macrolides, cephalosporins, linezolid, and doxycycline.[36][37][38] Even more common than the medications just mentioned include those over the counter, including ephedrine and synthetic cannabinoids.

Lastly, psychotropic medications and drugs of abuse must also be ruled out as the cause of hallucinations.[39] Upon ruling out hallucinations secondary to an underlying neurological condition or medication, the next step is confirming the presence of vision impairment or loss through a thorough ophthalmologic evaluation with visual field testing.[40]

Brain imaging may also be used to assess for impaired or loss of vision in individuals whose eye exam is unremarkable.[41] In summary, a diagnosis of CBS can be made in individuals having only visual hallucinations in the absence of neurologic abnormalities while in the presence of known vision impairment or loss.[42]

Treatment / Management

Treatment of CBS can vary depending on the severity of symptoms. In mild symptoms, reassurance may be all that is needed. However, in more severe symptoms, treatment includes behavioral techniques and medications to suppress hallucinations. Studied techniques include blinking during hallucination or rapid eye movement from one object to another away from the perceived hallucination field of vision.[22] The mainstay of management is physician awareness and compassion.[35][43]

Pharmacotherapy

Medications are often reserved for severe diseases, including those with disturbing or continuous hallucinations. Antipsychotics have been found to have mixed efficacy; however, atypical antipsychotics such as low doses of quetiapine or olanzapine are preferred due to safer side effect profiles, especially in the elderly CBS tends to affect.[44][33] 

Other medications with good efficacy and minimal side effects include cholinesterase inhibitors such as donepezil. Beneficial medications anecdotally include antiepileptics such as valproate, carbamazepine, gabapentin, and clonazepam. Lastly, some promising medications that are effective in small case series include antidepressants such as venlafaxine and escitalopram, as well as prokinetic agents like cisapride.[45][46]

Psychological Therapy

Various techniques such as hypnosis, relaxation training, distraction, cognitive remodeling, and psychological therapy for the phantom phenomenon have been advocated to minimize visual hallucinations' unpleasant and troublesome effects.[47]

Reassurance and Counselling

CBS patients may experience anxiety and are usually unaware of the condition. Many patients may show disappointment and unsympathetic reactions to meeting the healthcare professional regarding their hallucinations.[10] Reassurance is necessary as most patients are comforted when told that it's not a psychiatric phenomenon but is named CBS. The patients are also reassured that vision loss is benign and not harmful and there is no underlying mental illness.[48]

Patients with intact cognition need no further intervention, but patients having dementia may be difficult to reassure because of a lack of insight and vision loss of distressing nature. Reassurance and counseling are the mainstays of treatment.[49]

Optimizing Visual Function

This beneficial impact on hallucination may be the best treatment, although visual deficit correction may not always be possible, especially in elderly patients. The spectacle and visual aid prescription are necessary for optical correction, and cataract surgery may be necessary for visual correction.[2]

Differential Diagnosis

Essential considerations for differential diagnosis pertain to etiologies involving visual hallucinations. These include

• Narcolepsy
• Peduncular hallucinosis
• Levodopa-induced hallucinations
• Hypnagogic hallucinations
• Migraine coma
• Schizophrenia
• Epileptic seizures
• Dementia
• Migraine aura
• Neurodegenerative - Parkinson, Alzheimer, and Lewy body dementia
• Metabolic encephalopathy - drugs, alcohol withdrawal, or delirium

CBS is differentiated from all these conditions simultaneous presence of visual deficits and the absence of neurological deficits. Furthermore, CBS is differentiated by the lack of auditory or sensory-associated hallucinations, which can be seen in many of the above differentials.

Prognosis

The prognosis of CBS largely depends on the underlying cause of vision impairment or loss, with multiple symptoms associated with chronic ocular disease lasting multiple years.[14] 

One study highlighting this association found that 75% of patients with macular disease reported hallucinations for at least five years or more. In contrast, the prognosis is better in conditions where visual impairment can be quickly corrected, such as cataracts.[50][45] 

The prognosis of CBS can also be variable, with remitting visual hallucinations in those with slow progressing or stable vision impairment.[14] The individuals usually affected in this variable fashion are those affected by CVAs, with many having hallucinations lasting from a few weeks to a few days.[22]

Lastly, outside of the visual hallucinations associated with CBS, the condition has also been associated with the development of dementia. One study showing this association found that 26% of individuals with CBS developed dementia around an average of 33 months.[51]

Complications

CBS is described and understood as a transient condition not associated with significant adverse consequences or complications outside of worsening hallucinations. CBS complications mainly pertain to the psychological effects of the illusions experienced by patients.

Patients often fail to inform any medical staff or family and ultimately start believing they are becoming mentally ill. Further illustrating this phenomenon, a study in 2014 showed that approximately 32% of those with CBS are emotionally distressed from their hallucination.[14]

Consultations

Any patient presenting with hallucinations and vision loss should undergo a detailed evaluation by an ophthalmologist and a neurologist.[1] There should be a detailed assessment of neuropsychological status to pinpoint underlying pathology. It is highly imperative to rule out other causes of visual hallucinations.

The psychiatrist and the rehabilitation therapist also play an essential role in these patients. All patients should undergo a mini-mental state examination by a neurologist, and if needed, a psychiatric evaluation should be done if there is cognitive decline.[52]

Deterrence and Patient Education

Deterrence and patient education on CBS mainly relate to inquiring about visual hallucinations in those experiencing vision loss. Additionally, providing education on the condition from a primary prevention standpoint is also vital, given that many patients fail to report hallucinations due to the fear of being seen as mentally ill.[52] 

Studies have shown that education on CBS before the onset of hallucinations reduces negative symptoms such as fear or stress-related hallucinations impacting daily activities. For those who report hallucinations and meet diagnostic criteria, it is crucial to provide reassurance that CBS is primarily a transient condition unrelated to dementia or being mentally ill.[14]

Pearls and Other Issues

A detailed literature review reveals a lot of controversies and changing consensus over the inclusion and exclusion criteria for CBS.[53] Despite this disagreement, the management protocol remains the same. Despite the well-defined and strict diagnostic criteria, we usually overlook the clinical significance of CBS, as visual hallucinations can occur in patients with visual impairment. CBS patients are typically elderly and are usually depressed by their visual acuity, the nature of which is not understood by these patients. If attention is not pain, CBS can be misdiagnosed and inappropriate treatment.[1]

Another essential thing to be kept in mind is that the majority of information on CBS is detailed in psychiatric literature than ophthalmic literature. If the patients present with hallucinations, they are labeled as mentally unstable and referred to a psychiatrist.[54]

To an ophthalmologist, these patients present with visual impairment, as most suffer from defective vision. Even the first described patients, Lullin and Bonnet, presented with ocular pathology, and the ophthalmologists rarely encountered these patients with visual hallucinations.[2]

CB-type visual hallucinations without a visual loss should be labeled as separate entities. Cognitive decline is another contributory factor but is rarely the primary etiological factor. The most widely accepted definition of CBS is sensory deprivation-deafferentation- of the cerebral cortex and release phenomenon of hallucinations. CBS may mimic Alzheimer and Parkinsonism as cognition is impaired in all these conditions.[6]

Enhancing Healthcare Team Outcomes

Enhancement of healthcare team outcomes on CBS primarily revolves around primary care working with interdisciplinary fields such as ophthalmology, neurology, and psychiatry. When patients can be appropriately assessed and meet diagnostic criteria for CBS, providing education and reassurance on the condition is often all that is needed to reduce anxiety, concerns, and other adverse outcomes related to CBS.[18]

Interprofessional care coordination is also necessary for managing CBS. Pharmacists can provide information regarding potential medication causes for the patient's presentation. Nurses can assist with examinations, perform patient counseling, and serve as care coordinators among various practitioners.

All interprofessional team members are tasked with providing accurate records of their interactions and interventions with the patient. They need to be empowered to contact other team members if they have any concerns about the patient's condition or note any status changes. This interprofessional model will provide the best opportunity for a positive outcome. [Level 5]