Clinical manifestations

Presentation and course

From a definitional perspective, patients with phosphenes (ie, unstructured lights such as flashes, sparkles, zig-zag lines), photopsias (ie, simple structured images such as geometric figures occurring in a repetitive pattern), and complex visual hallucinations (eg, people, animals, landscapes) have similar lesions on brain imaging (136), suggesting that there is no anatomic area unique for each type of "positive spontaneous visual phenomena." Thus, limiting the definition of Bonnet hallucinations to complex visual hallucinations has no clear localizing value or etiologic specificity (103; 16; 139). As a result, most now accept that these hallucinations can include simple or complex hallucinations, including geometric shapes, animals ("zoopsias"), human figures, buildings, or landscape scenes (109; 22; 07; 75; 112; 103; 79; 37; 64).

Bonnet hallucinations are usually well-defined and clear, complex and often elaborate, repetitive, stereotyped visual hallucinations restricted to a single modality, ie, visual hallucinations only without associated olfactory, gustatory, auditory, or tactile hallucinations (60). They may appear suddenly, are not under voluntary control, are persistent though usually intermittent, and are simultaneous bilateral phenomena (13). The hallucinations may be stationary or in motion (Schwartz and Melzack 1991; 112; 64; 104), altered in size (eg, small or "Lilliputian" figures), sometimes grotesque or distorted (103), and are frequently chromatic (colored, and often multicolored) (128; 75; 85; 139; 64; 13). The most common hallucinations are of people or animals (64; 104).

Patients generally have full or partial retention of insight, without delusions or psychosis, and without associated intoxication or withdrawal (60). The hallucinations are generally neutral or pleasant and nonthreatening but may cause distress, especially as patients are aware that the visual images are not "real" (109; 22; 129; 128; 132; 07; 112; 78; 123; 124; 139; 137; 24; 101). The content of the hallucinations has no personal meaning for affected patients (130). Nevertheless, the emotional response to the hallucinations is typically congruent with the hallucinatory content; for example, hallucinations of a macabre nature typically produce a fearful response (58). Factors associated with negative outcomes include: (1) frequent, fear-inducing, longer-duration hallucinations; (2) evident impact on daily activities; (3) misattribution of hallucinations to mental illness; and (4) inadequate knowledge of Bonnet syndrome at symptom onset (24).

The frequency of Bonnet hallucinations may range from daily to weekly (85; 104; 135), and the duration of individual hallucinations is usually a few minutes but may be shorter or longer, from seconds up to a full day (109; 111; 07; 85; 104; 135). Episodes can occur for days to years, with changes in complexity and frequency over time (109; 104). However, most episodes last days to months (136).

Triggers for Bonnet hallucinations can include low light levels, fatigue, and emotional stress (109; 128). Bonnet hallucinations often occur with eyes open and disappear with eyes closed. Some patients can terminate their hallucinations by closing or opening their eyes, attempting to fixate vision on or away from the hallucination, or making saccades to one side or the other (66; 128; 136).

Bonnet syndrome frequently goes unrecognized in clinical practice due to providers’ lack of awareness and patients' reluctance to report hallucinatory experiences (38; 137). Some patients are afraid to report such hallucinations to their physicians because they are concerned that these indicate mental illness or the incipient development of dementia, and, therefore, that reporting such experiences will compromise their autonomy (58). Many affected patients express relief when informed that such hallucinations are relatively benign and unrelated to insanity or dementia.

Patients with progressive bilateral prechiasmal visual loss often develop Bonnet hallucinations as visual acuity declines, but these hallucinations typically resolve after development of total blindness (115; 38). At least in some patients, an acute or subacute reduction in visual acuity appears to be more important than static low visual acuity per se (115). In patients with age-related macular degeneration, the extent of visual loss does not predict the likelihood of developing Bonnet syndrome, nor does the progression of loss reflect in the complexity of the hallucinations reported (01).

Although Bonnet syndrome is most commonly identified in patients with bilaterally decreased central visual acuity (95), similar phenomena also occur in patients with retrochiasmal visual field defects (15; 110; 37; 20; 36; 125; 05; 23; 62; 18; 67; 106), and even in patients with visual field defects and normal central visual acuity (37; 125; 74). Bonnet hallucinations in patients with retrochiasmal visual field defects occur most commonly in patients with cerebral infarcts involving the optic radiations or primary visual cortex but may also occur in other circumstances, eg, after antero-mesial temporal lobe resection for epilepsy (23), or with occipital falx meningiomas (106). Visual hallucinations are typically restricted to the abnormal visual field in patients with visual field defects. Retrochiasmal lesions associated with hallucinations are typically smaller than those causing hemianopsia without associated Bonnet hallucinations and frequently spare visual association cortex, whereas large lesions destroying anterior visual association cortex appear to preclude development of such hallucinations, suggesting that some intact visual association cortex is necessary to experience these complex hallucinations (136). Onset in central cases is generally within a few days of the event causing the defect (66).

A similar phenomenon may be responsible for visual hallucinations in the Heidenhain variant of Creutzfeldt-Jakob disease, which is characterized by isolated visual disturbances at disease onset, including complex visual hallucinations, which reflect the early involvement of prions in the occipital cortex (87; 11; 94; 40; 102; 134; 120; 140).

The relationship between Bonnet syndrome and cognition is not entirely clear because some elderly patients with Bonnet syndrome subsequently develop dementia. In a pilot cohort study of people over age 65 with Bonnet syndrome and age-matched controls, two of 12 cases and no controls developed dementia (101). Both cases that developed dementia had partial insight and hallucinations of familiar figures at the time of diagnosis of Bonnet syndrome, and one had mild cognitive impairment. Further larger cohort studies will be needed to determine whether elderly patients with Bonnet syndrome have an increased risk of developing dementia.

Prognosis and complications

Postsurgical cases are generally transient and resolve between 4 days and 6 months postoperatively, even with persisting visual field deficits (37; 23). Because of the benign nature of the phenomena, and the self-limited course, such postoperative hallucinations do not usually require treatment (23).

Some have suggested that Bonnet syndrome may be an early marker for dementia (92; 44), though most studies do not indicate any cognitive impairment in most patients with Bonnet syndrome (09; 110; 133).

Systematic longitudinal cognitive evaluations on large samples of patients with Bonnet syndrome have yet to be performed. Preliminary data suggest that the hallucinations will resolve within 1 year in more than a quarter of those who develop Bonnet hallucinations (54).

Clinical vignette

James Thurber and Bonnet syndrome. In Phantoms in the Brain: Probing the Mysteries of the Human Mind (1998), psychologist and neuroscientist Vilayanur Ramachandran MBBS, PhD suggested that the American author, humorist, and cartoonist James Thurber (1894-1961) had Bonnet syndrome (96; 48).

When Thurber was 6 years old, his older brother, William, accidentally shot an arrow into his left eye, reportedly while playing “William Tell.” His injured eye was not immediately removed, and vision in Thurber’s undamaged right eye soon became impaired because of sympathetic ophthalmia. Sympathetic ophthalmia is a bilateral, granulomatous uveitis that can occur after trauma to one eye, presumably due to an autoimmune mechanism. The condition is vision-threatening, and many patients end up with significant bilateral vision loss, especially if treatment is not instituted quickly. Prevention is limited to urgent closure of the traumatized eye and enucleation within 10 to 14 days after the traumatic event. Thurber’s injured left eye was eventually removed, but by then, vision in his uninjured right eye was also permanently impaired, and he was going blind by 1937.

Ramachandran wrote that as an adult with severe visual impairment, Thurber described numerous vivid visual hallucinations in correspondence with his ophthalmologist:

Ramachandran also described additional Thurber visions:

These visual hallucinations in the setting of severely impaired vision in an otherwise mentally healthy person are consistent with Bonnet hallucinations. Ramachandran suggested further that Thurber's vivid imagination may be partly explained by having had Bonnet syndrome.

Biological basis

Etiology and pathogenesis

Bonnet hallucinations are caused by bilateral blindness, usually a severe to profound loss, most commonly related to retinal disease, usually age-related macular degeneration and glaucoma (104; 83). Other causes of blindness can also produce Bonnet hallucinations, including retinitis pigments, anterior ischemic optic neuropathy, toxoplasmic retinochoroiditis, etc. (135). Related phenomena are caused by homonymous visual field defects resulting from interruption of visual input to the occipital cortex.

The complex nature of Bonnet hallucinations indicates that they are generated in the visual association cortex (37). The development of visual hallucinations in patients with hemianopia after stroke is inversely correlated with lesion size and specifically requires a relatively small lesion that includes loss of the striate cortex but that spares Brodmann areas 19, 20, and 37 (76).

Visual pathway lesions can cause hallucinations from defective visual processing or abnormal cortical activity (75). The specific pathophysiological mechanisms involved in Bonnet syndrome are still being investigated, but many authors have suggested a "release" mechanism associated with modality-specific sensory deprivation or deafferentation (117; 109; 110; 16; 79; 78; 37; 95; 20; 125; 55; 17). Some have referred to this as "phantom vision" akin to phantom limbs in patients with loss of somatosensory input after an amputation (109; 84; 78). In support of a release mechanism for Bonnet hallucinations, sensory deprivation and a low level of arousal favor development of the hallucinations but are not required for their development (128). It may occur even with transient vision loss, as with eye patching, in susceptible individuals (55).

Cogan distinguished "irritative" and "release" hallucinations in patients without psychosis (21). An "irritative" mechanism for hallucinations is supported by any of the following: (1) stereotyped content; (2) lack of awareness of the hallucinatory nature of the perception ("hallucinosis"); and (3) evidence of an irritative process (eg, migraine, tumor, seizures) (21; 12). In general, a "release" mechanism for hallucinations is supported by (1) a sensory deficit in the same modality as unimodal hallucinations, with onset of hallucinations in conjunction with or following the sensory deficit; (2) variable content; (3) awareness of the hallucinatory nature of the perception; and (4) no evidence of seizures or other irritative phenomena (including no other positive motor or sensory phenomena, not paroxysmal in character, and no epileptiform discharges on electroencephalography) (21; 72; 12). Release hallucinations can occur in normal individuals with pansensory deprivation (51; 50). Similarly, modality-specific release hallucinations can occur experimentally (50; 77) or pathologically (49; 72; 71) with unimodal sensory deprivation. In support of a release mechanism for Bonnet hallucinations, sensory deprivation and a low level of arousal favor development of the hallucinations but are not required for their development (128).

Presumably, a generative model exists in the brain that can synthesize consistent visual representations even without actual visual input (100). Homeostatic regulation of neuronal activity could make the learned internal model robust against degradation of sensory input, but it may overcompensate in the case of Bonnet syndrome, leading to hallucinations (100).

Deafferentation produces an increase in excitability of the deafferentated neurons and an increase in spontaneous activity (29; 69; 31; 16). High-frequency bursts of synchronized though nonepileptic neural activity in areas of deafferentated cortex may be necessary for these hallucinations (16).

SPECT studies of patients with Bonnet syndrome have shown hyperperfusion in the lateral temporal cortex, striatum, and thalamus, presumably representing the results of central nervous system plasticity and compensation (02). In one case, positron emission tomography-statistical parametric mapping studies initially showed hypermetabolism in the right inferior temporal area and left thalamus, which disappeared after treatment with valproic acid (57). Functional magnetic resonance imaging studies indicate that Bonnet hallucinations are associated with increased ventral extrastriate activity, which persists even between hallucinations (35). The location of increased activity correlates with the type of hallucination, with color associated with activity in the posterior fusiform area, faces associated with activity in the left middle fusiform area, objects associated with activity in the right middle fusiform area, and textures associated with the collateral sulcus (35). The relative frequency of certain complex forms (eg, faces) may reflect the amount of association cortex devoted to representing these forms or the magnitude of the distributed network processing such forms (69; 139).

An informative case was presented by Sasaki and colleagues (106). A 74-year-old man presented with complex visual hallucinations with a left inferior quadrantanopia, due to a right occipital falx meningioma. Fusion images of gadolinium-enhanced MRI and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) of the brain demonstrated hypometabolism in the right primary and secondary visual cortices and an ipsilateral hypermetabolism in a focal area of the medial aspect of the secondary visual cortex as well as the lateral part of the ventral visual pathway. Presumably, this hyperactivation of the ventral visual pathway, especially the lateral aspect of the ventral occipitotemporal cortex, was "released" by the inactivity of the corresponding primary visual cortex due to mass effect from the meningioma.In some cases, transient dynamic changes in visual acuity can precipitate or relieve the hallucinations. Bonnet hallucinations have been reported during visual recovery after central retinal artery occlusion (126). Acute severe anemia can precipitate worsened vision and Bonnet hallucinations in some patients (eg, bilateral retinal vein occlusion), and rapid visual acuity improvement and reversal of hallucinations may follow blood transfusion (61). Bonnet hallucinations may occur even with transient loss of vision, as with eye patching, in susceptible individuals (63; 55).

A variant disorder, labeled the "Charles Bonnet plus syndrome" or "Charles Bonnet syndrome plus," involves multimodal hallucinations resulting from deafferentation in more than one sensory modality. For example, a patient with Usher syndrome (a genetic syndrome characterized by progressive loss of vision and hearing) experienced complex visual hallucinations and musical auditory hallucinations ("cabaret music") (114).

Although deafferentation remains the best available pathophysiological explanation for Bonnet hallucinations, deafferentation alone seems insufficient as it fails to explain the absence of hallucinations in the majority of patients with severe bilateral visual impairment (33).

Epidemiology

Visual dysfunction is associated with an increased likelihood of hallucinations in the older U.S. adult population: hallucinations are more prevalent in those with difficulty reading newspaper print or recognizing someone across the street (43).

Estimates of the prevalence of Bonnet syndrome range widely in different samples depending on the distribution of severe bilateral vision loss in the group studied and the specific disease definition or diagnostic criteria (129; 85; 37; 116; 104; 107). Among general ophthalmologic and optometric patients, the frequency is about 0.5% (116), but higher in patients with low vision and the elderly (129; 116; 64; 53; 104). Higher rates are seen in patients with severe glaucoma (85; 60; 90), macular degeneration (64; 104; 60), or other low vision caused by anterior visual pathway dysfunction (129; 138; 60), and in postoperative patients following lesions of the retrochiasmal visual pathways (37). In a metaanalysis, the prevalence of Bonnet syndrome was 2.8% among patients with glaucoma in different stages and with ocular comorbidities, 13.5% among patients with glaucoma and bilateral low visual acuity, and 20.1% among patients with glaucoma who visited vision rehabilitation clinics, presumably due to extensive vision impairment (122). The prevalence of Bonnet syndrome in patients with late age-related macular degeneration is high, with estimates of 8% to 58% (64; 137; 119; 104; 73). Similar values are reported in other populations of elderly patients with severe bilateral vision loss (138). Prevalence does not differ significantly by the cause of the visual problem when patients of similar age and degree of visual impairment are compared (38).

Besides low vision, risk factors for (a diagnosis of) Bonnet syndrome include advanced age, female gender, reduced contrast sensitivity, and not living alone (122).

Bonnet syndrome frequently goes unrecognized in clinical practice due to a lack of awareness among providers and patients' reluctance to report hallucinatory experiences for fear of being labeled as mentally ill (117; 128; 85; 78; 123; 24; 135).

Although most cases are elderly, Bonnet hallucinations may also occur in children and adolescents (59). Most of these have progressive inherited retinal diseases, primarily Stargardt disease, a rare genetic eye disease associated with deposition of fatty material in the macula (59). Mutations in the ABCA4 gene usually cause Stargardt macular degeneration, but, less often, it may be caused by mutations in the ELOVL4 gene. Other reported pediatric disorders can also cause this, including juvenile neuronal ceroid lipofuscinosis (71).

Poor visual acuity is the most important factor associated with developing of Bonnet hallucinations (64). Although Bonnet hallucinations can affect people of any age, including children (105), it is much more common in elderly patients (129; 07; 34; 02; 19; 78; 56; 91; 116; 124; 20; 01; 65). Medications, such as proton-pump inhibitors, can increase the risk of developing visual hallucinations independently of the degree of visual loss in patients with age-related macular degeneration (73).

Differential diagnosis

Confusing conditions

The differential diagnosis of visual hallucinations is broad. In the elderly, who are most susceptible to Bonnet hallucinations, visual hallucinations are commonly reported in the absence of significant visual impairment in patients with psychosis, medication-induced hallucinosis, delirium, delirium tremens, Parkinson disease, Lewy body dementia, and Alzheimer disease.

The main consideration is separating visual hallucinations associated with bilateral visual loss (Bonnet hallucinations) from visual hallucinations associated with psychiatric disorders, delirium, or dementia. Cognitive impairment alone can be associated with visual hallucinations, even without visual impairment. It seems likely, though, that cognitive impairment can facilitate the development of visual hallucinations in those with visual impairment (and vice versa) (46; 68). Visual hallucinations are commonly observed in patients with synucleinopathies such as Parkinson disease and Lewy body dementia; in these disorders, the visual hallucinations result from a combination of the underlying pathology as well as the dopaminergic medications used to treat these disorders.

A few authors have also reported what were labeled as Bonnet hallucinations following administration of a medication, which then resolved on medication withdrawal; however, these are probably cases of medication-induced visual hallucinosis, and in general, such cases should not be considered as cases of Bonnet syndrome.

Patients with retrochiasmal visual pathway dysfunction (eg, homonymous hemianopsia), who develop intermittent complex visual hallucinations, may instead have partial seizures (86; 14). Although some authors have considered epileptic visual hallucinations as an epileptic form of Bonnet syndrome (86; 14), this is conceptually problematic, and such terminology should be discouraged.

Diagnostic workup

Although the diagnostic evaluation is usually straightforward in Bonnet hallucinations, they remain commonly underreported, underrecognized, and misrecognized (60). Visual hallucinations in conjunction with significant bilateral visual loss should raise clinical suspicion for Bonnet hallucinations. The visual loss should then be localized to the eyes, optic nerves (06), chiasm (91; 53), or retrochiasmal visual pathways based on ophthalmoscopy, pupillary reactions, and visual fields. With history and examination, establishing a localization for the visual loss and a specific etiologic diagnosis will often be possible. Ophthalmology referral is appropriate for patients with ocular pathology (eg, cataracts, glaucoma, macular degeneration, diabetic retinopathy). Neuroimaging is often needed to establish or support an etiologic diagnosis with retrobulbar visual loss localized to the optic nerves (eg, demyelinating disease), optic chiasm (eg, pituitary tumors), or retrochiasmal visual pathways (eg, cerebrovascular disease). Further evaluation is dictated by the history, the identified locus of the visual impairment, and the results of neuroimaging.

Management

Patients and their families generally respond favorably to education concerning the nature of the hallucinations and supportive counseling. It is important to emphasize that the phenomenon is common, benign, related to visual impairment, and not indicative of dementia, psychosis, or serious underlying neurologic disease.

There is no definitive treatment available for Bonnet syndrome, although various ophthalmologic interventions, behavioral strategies, and pharmacologic agents have been used to try to reduce or relieve symptoms (45).

Bonnet hallucinations may terminate spontaneously, on improving or stabilizing of visual loss (eg, with glasses, cataract surgery, laser treatments, low-vision devices, etc., as appropriate to the clinical circumstances), with use of improved lighting, or on improving grief, loneliness, or social isolation (04; 130; 132; 07; 127; 78; 30; 56; 25; 118). Treatment, therefore, should focus initially on correcting visual function, using adaptive equipment as necessary, as well as ensuring adequate lighting and increasing social interaction and engagement (25; 108; 118).

Some patients are afraid to report such hallucinations to their physicians because they are concerned that these indicate mental illness or development of dementia (85; 78; 123; 139; 137; 82). Reassurance is, therefore, one of the mainstays of treatment (108). Many patients with Bonnet hallucinations express relief when informed that such hallucinations are relatively benign and unrelated to insanity or dementia (128; 07; 56; 123; 108).

In some cases, medications seem to precipitate the hallucinations, and such hallucinations respond to withdrawal of the medications (32; 131; 113). However, it is often unclear if these are simply cases of medication-induced visual hallucinosis (95) and should not generally be considered cases of Bonnet syndrome. A different circumstance occurs when Bonnet hallucinations develop in patients with severe age-related macular degeneration after intravitreal injections of bevacizumab (an angiogenesis inhibitor): in such cases, reduced retinal edema and temporarily altered visual acuity may promote the release phenomenon and trigger Bonnet hallucinations (80).

A wide range of pharmacological treatments have also been reported to alleviate Bonnet hallucinations, but almost all of these are anecdotal, being based on small samples (often single cases) in uncontrolled trials (30). There is no universally effective drug treatment (07; 78). Such hallucinations are generally not resolved or improved with anticonvulsants or antipsychotic medications (07; 30; 20), although there are anecdotal reports of occasional patients that seem to respond to anticonvulsants, atypical antipsychotic medications, or selective serotonin reuptake inhibitors (07; 97; 52; 03; 78; 30; 89; 70; 113; 18; 41). Other agents have been anecdotally reported to be effective in isolated patients, including acetylcholinesterase inhibitors (133). In rare cases of Bonnet syndrome associated with visual impairments from temporal arteritis, steroid treatment can result in prompt resolution of visual hallucinations, even with persistent visual loss (121; 99); the implications of this are not fully clear but may suggest other mechanisms may be involved in the continuation of such hallucinations beyond simple "release" mechanisms. Tricyclic antidepressants and benzodiazepines have not been helpful (07).

More complicated interventions have also been explored in pilot studies, including inhibitory transcranial direct current stimulation of the visual cortex (26), but this has not been proven with adequate controlled trials.