Version May 2024
INTRODUCTION — The Charles Bonnet syndrome (CBS) refers to symptoms of visual hallucinations that occur in patients with visual acuity loss or visual field loss. These are often called release hallucinations, reflecting the most widely accepted theory of their pathogenesis.
Underlying conditions of vision loss associated with the CBS affect the eye, optic nerve, or brain and include a diverse set of pathologies, such as macular degeneration and stroke. While often not functionally disabling, the hallucinations can be distressing to patients and negatively impact quality of life [1]. Published case reports suggest that the syndrome is not well recognized by clinicians and may often be misdiagnosed as psychosis or early dementia [2,3].
The pathophysiology, causes, clinical features, diagnosis, and treatment of the CBS will be reviewed here. Other causes and the overall approach to visual hallucinations are discussed separately. (See "Approach to the patient with visual hallucinations".)
EPIDEMIOLOGY — The CBS may be more common than is generally appreciated. Visual hallucinations are often unreported by patients because they fear that they represent psychiatric disease [1,4,5]. When this symptom is specifically solicited in older patients with impaired vision, 11 to 15 percent admit to having visual hallucinations [1,5-12]. These surveys also reveal that most patients had failed to report these symptoms to their clinician or to family members. One study found that only 12 percent of patients attending a retinal clinic were aware of the condition [13].
Patients with more significant vision loss may be more likely to experience and report visual hallucinations. In one survey of patients diagnosed with macular disease, the reported prevalence was 39 percent [14], and among patients with glaucoma attending a visual rehabilitation program, the prevalence was 20 percent [15].
Release hallucinations have been reported in all age groups, including children [9,16]. However, most patients with CBS are older adults; in large case series, the mean age is between 70 and 85 years [4,9,17,18]. This probably reflects the mean age at which the most common underlying conditions causing vision loss are seen. Some investigators, but not others, have found that advanced age is a risk factor for release hallucinations within their study population [7,12,19].
Other conditions that are inconsistently found to be risk factors for CBS include cognitive impairment, cerebrovascular disease, cortical atrophy on brain imaging, and social deprivation [7,8,18-22].
PATHOPHYSIOLOGY — Patients with visual acuity loss or visual field loss from any cause, affecting any part of the visual pathway from the eye to the visual cortex, can develop visual hallucinations [4]. Common underlying conditions include age-related macular degeneration, glaucoma, diabetic retinopathy, and cerebral infarction [1,4,5,9,14,23]. However, these hallucinations have been reported to occur in virtually every acquired disorder affecting the visual system [9]. CBS does not occur with congenital blindness.
The most widely accepted theory is that the hallucinations occur when visual sensory deafferentation leads to disinhibition of visual cortical regions, which then fire spontaneously [17,24-26]. Similar hallucinations have been reported by individuals subjected to visual deprivation experiments [9]. Functional neuroimaging studies offer some support for this theory [20,27,28]. In four patients with CBS, functional magnetic resonance imaging revealed that active hallucinations were associated with spontaneous activity in the ventral occipital lobe [27]. The content of the hallucinations was associated with specific regional activation that correlated with the known specialized function of that area of the visual cortex.
The neurobiology underlying visual hallucinations in CBS remains to be elucidated. In other settings, outside the visual system, deafferentated neurons have been associated with a variety of biochemical, morphologic, and neurophysiologic changes that suggest a phenomenon of denervation hypersensitivity [25].
CLINICAL FEATURES
Association with underlying visual disorder — CBS may occur in association with acute or chronic ocular disease.
●For patients with chronic ocular disease, the diagnosis of ocular disease is generally established for at least one year before hallucinations emerge [1,8,9]. The likelihood of release hallucinations increases with lower visual acuity [4,19]. While there is no clear threshold of visual acuity loss, the prevalence of hallucinations appears to increase with acuity worse than 20/60 [7,8]. CBS is also more likely to occur with binocular versus monocular disease [1,8,9].
●By contrast, when release hallucinations occur in the setting of acute cerebral or optic nerve injury (eg, optic neuritis, stroke, surgery), they often occur concomitantly with the vision loss or after a latency of a few hours or days [10,23,29-32]. Latencies of more than several months have also been reported [33-36]. A large visual field deficit is not required [10].
Content of hallucinations — Release hallucinations can be simple, nonformed images such as lines, light flashes, or geometric shapes, or they can be complex, formed images of people, animals, or scenes [19,24,29,31]. In a series of 59 patients with release hallucinations due to loss of vision from retinal or neurologic causes, simple hallucinations were more common than complex hallucinations (90 versus 37 percent) [19]. The location of injury within the visual system did not determine the nature of the hallucinations. Others report a higher proportion of complex hallucinations [1]. The content of the simple or complex hallucinations is variable, even for individual patients [4,5,9]. Although some patients perceive the same hallucination each time, they usually do not recur in a stereotyped fashion, a feature that distinguishes them from epileptic hallucinations.
There are no associated auditory or other sensory modality hallucinations.
The images are usually colored and may be static, animated, or move en bloc across the visual field [5,8,9]. The location of the hallucinations typically corresponds to the underlying vision loss, and as a result, can be monocular or binocular and/or restricted to one-half of the visual field [19,23,29,31,37].
The content of the hallucinations usually does not have emotional impact or personal meaning for the patient who almost always recognizes them as unreal [1,4,5,19]. Despite this, a significant number of patients are distressed by their symptoms [14,23].
Other features — Hallucinations occur more often with the eyes open than closed [4], and patients often describe seeing the hallucinations when they are looking at a white background such as a wall, ceiling, or piece of paper. The hallucination will often disappear if the patient closes his or her eyes or looks away [29]. In one study of 60 patients with CBS, most complex hallucinations occurred in the setting of sensory deprivation (eg, dim lighting, inactivity, being alone) and in the evening or nighttime [4].
The duration of the hallucination ranges from less than one minute to continuous [1,4,5,8,38]. Most patients report a duration of several minutes. The frequency is variable; the majority of patients experience hallucinations multiple times a day or week [1,5,23]. Some patients experience only a few isolated episodes.
Associated symptoms depend upon the underlying disorder producing the visual loss. As examples, strokes involving the visual pathways produce visual field loss and sometimes other neurologic deficits, while macular degeneration and diabetic retinopathy produce loss of visual acuity without neurologic deficits [23]. Patients with CBS typically do not have an abnormal mental status or other neurologic deficits [22]. However, a syndrome of agitated delirium, visual hallucinations, and hemianopia can also be produced by lesions (usually stroke) affecting the medial aspect of the occipital lobe, the parahippocampal gyrus, and the hippocampus [23]. This can be difficult to distinguish from acute toxic metabolic encephalopathy. (See "Approach to the patient with visual hallucinations", section on 'Metabolic encephalopathy'.)
DIFFERENTIAL DIAGNOSIS — Other etiologies of visual hallucinations include:
●Migraine aura
●Epileptic seizures
●Neurodegenerative disease, especially dementia with Lewy bodies and Parkinson disease
●Drugs, alcohol intoxication or withdrawal (table 1)
●Metabolic encephalopathy, delirium
●Peduncular hallucinosis
●Narcolepsy
●Psychiatric disease
In general, CBS is distinguished from these entities by the absence of other neurologic deficits and by the presence of known ocular disease. Characteristics of the hallucinations and associated symptoms can also help distinguish these causes from the release hallucinations of CBS (table 2). (See "Approach to the patient with visual hallucinations", section on 'Etiologies'.)
DIAGNOSIS — All patients with new-onset visual hallucinations should have a complete neurologic evaluation screening for cognitive impairment, parkinsonism, and other neurologic deficits, and the medication list should be reviewed. Drugs and medications associated with visual hallucinations are listed in the table (table 1). In the absence of other neurologic abnormalities, and in the setting of known ocular disease (eg, macular degeneration), further diagnostic evaluation may not be required.
By comparison, in the absence of known eye disease, a complete ophthalmologic evaluation with visual field testing should be performed. Brain magnetic resonance imaging is indicated if there is a visual field deficit or other focal neurologic deficit and for patients in whom the cause remains obscure.
Patients with atypical features for CBS should also be further evaluated (table 2). As examples:
●Patients with abnormal mental status should be evaluated for psychiatric disease and/or delirium with laboratory studies and toxicology screen.
●Associated auditory and/or tactile hallucinations are not consistent with CBS and suggest possible psychiatric disease, peduncular hallucinosis, narcoleptic hallucinations, or hearing or sensory loss.
●Brief hallucinations that recur in a stereotyped fashion may indicate electroencephalography (EEG) to evaluate for possible seizure disorder.
The general diagnostic approach to patients with visual hallucinations is discussed in detail separately. (See "Approach to the patient with visual hallucinations", section on 'Evaluation'.)
PROGNOSIS — Release hallucinations often resolve if the underlying vision deficit is corrected, as with cataract removal [9,39-41]. Hallucinations can also remit in some patients with either static or progressive vision loss. This appears to occur more often for patients with acute cerebral injury (stroke, surgery), in whom hallucinations often last only several days to a few weeks [10,23,30,31]. However, such patients, as well as those with chronic ocular disease, can experience persistent hallucinations over several years. In one survey of patients with release hallucinations associated with macular disease, 75 percent had symptoms lasting five years or more [14].
Patients may be concerned that their symptoms may represent incipient dementia. We reassure patients that that is not the case. While one small series found that 26 percent of patients with CBS developed dementia over an average 33 months of follow-up [42], further study is necessary to understand the magnitude of the associated risk [22].
TREATMENT — Treatment is individualized according to the degree the patient is disturbed by their symptoms. While many find that symptoms have no significant impact on their life, up to a third of patients in one series reported that symptoms were distressing and had a negative effect on their quality of life [14].
I have found that patients are often relieved to know that treatment is an option. This reassurance may be all that is required [5]. Some patients can be taught to suppress the hallucinations. Rapid eye movements from one target to another, particularly away from the affected visual field, or blinking may temporarily suppress the hallucination [23,29,43]. Increasing arousal and visual stimuli (eg, increased illumination) and reducing social deprivation are also reported to be useful for individual patients, but these techniques have not been systematically studied [44,45].
Patients with continuous hallucinations or those with disturbing imagery may need specific treatment. While antipsychotic medications are sometimes cited as ineffective, others report benefit in individual patients [3,33,41,46,47]. Newer (atypical) antipsychotic agents have fewer side effects than conventional agents, particularly in the older adult population. I have found that low doses of olanzapine or quetiapine provide benefit without significant side effects. In my experience, cholinesterase inhibitors (eg, donepezil) also can provide some relief with minimal side effects [48]. Antiseizure medications (carbamazepine, clonazepam, valproate, and gabapentin) are also helpful in anecdotal reports [35,40,49-53]. Individual case reports and small series also report benefit with escitalopram, cisapride, and venlafaxine [32,54,55]. Even partial relief may provide benefit for patients who desire treatment.
SUMMARY AND RECOMMENDATIONS
●Definition – Charles Bonnet syndrome (CBS) refers to a phenomenon of visual hallucinations occurring in patients with acquired vision loss affecting the eye or visual tracts in the optic nerve, chiasm, or brain.
●Risk factors – CBS is most common among those with worse visual acuity and older age. Cognitive impairment and living conditions of sensory deprivation are not clearly risk factors. (See 'Epidemiology' above.)
●Clinical features – The hallucinations of CBS may be elementary (unformed flashes of light or geometric shapes) or complex (formed images often of animals, people, or scenes).
These typically last a few minutes and usually recur frequently, daily or weekly. (See 'Clinical features' above.)
●Diagnosis – The diagnosis of CBS is made when visual hallucinations occur in patients with vision loss in the absence of psychosis, delirium, or other causes.
When there is no known history of vision loss, evaluation should include toxicology screen, ophthalmology consult, neurologic evaluation, visual field testing, and/or brain imaging. (See 'Diagnosis' above.)
●Management – Reassurance is important and may be all that is required; however, treatment should be offered as well.
Patients may be able to temporarily suppress hallucinations by closing their eyes or looking away.
If hallucinations are troubling to patients, we suggest treatment trials with low doses of atypical antipsychotics, cholinesterase inhibitors, serotonin reuptake inhibitors, or antiseizure medications, all of which have anecdotal evidence of efficacy (Grade 2C). The choice of medication is guided by side effect profiles and patient comorbidities. Even partial alleviation of the hallucinations can bring relief to patients with troubling hallucinations. (See 'Treatment' above.)
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
