Charles Bonnet Syndrome 

Charles Bonnet Syndrome – 21 Interesting Facts

1. Charles Bonnet syndrome (CBS) is defined as visual hallucinations, usually complex and not distressing, in patients without psychiatric or cognitive conditions
2. Complex visual hallucinations may feature vivid, complicated images of people, animals, or plants
3. Retained insight into unreal nature of visual hallucinations is a defining characteristic of CBS
4. Recurrent hallucinations may continue for days to years
5. Reported prevalence varies greatly from < 1%-30% in patients with eye disease and/or vision loss with high variance, likely due to lack of consistent diagnostic criteria, reluctance of patients to report symptoms, different ascertainment populations
6.  CBS most often affects older adults (> 70 years old) with visual impairment due to ophthalmologic conditions
7. lesions at any level of the visual pathway may cause CBS
8. common causes include age-related macular degeneration, glaucoma, and cataracts
9. underlying pathophysiology not entirely understood, however deafferentation theory (reduced visual input leading to increased spontaneous activity in visual cortices) is the most widely accepted theory
10. suspect CBS in patients with visual hallucinations and both
11. lack of psychiatric and cognitive impairments
12. retained insight into unreal nature of visual hallucinations
13. perform diagnostic testing in patients with suspected CBS to
14. evaluate for possible ophthalmologic conditions
15. rule out alternate causes of visual hallucinations
16.  no standard treatment currently exists for CBS; management should include reassurance that CBS is benign and not a precursor to mental instability or dementia
17. other management options to consider include
18. taking appropriate steps to correct vision in patients with vision impairment, such as corrective lenses and low-vision rehabilitation
19. treating underlying ophthalmologic condition, including surgery if appropriate
20. modifying patient’s environment, such as by increasing light levels, if visual hallucinations are associated with specific environmental conditions, such as dim lighting
21. taking other practical actions reported to stop hallucinations, such as rapid blinking and concentrating on something else. If visual hallucinations are continuous and distressing, consider medications reported to reduce symptoms and hallucinations, such as antipsychotics, antiseizure medications, or selective serotonin reuptake inhibitors (SSRIs)

Introduction

•  Charles Bonnet syndrome (CBS) is characterized by visual hallucinations, usually complex and not distressing, in patients without psychiatric or cognitive conditions
•  CBS patients usually have insight that the hallucinations are not real
•  CBS often associated with visual impairment due to ophthalmologic conditions such as glaucoma, cataracts, and macular degeneration ^(1,2,3)

Synonyms

•  Phantom vision syndrome
•  Visual release hallucination

Definitions

• visual hallucinations – perception of external visual stimulus where none exists^(1,2,3)
  • complex hallucinations (also described as formed)
    •  feature realistic scenes and vivid and complicated images of people, faces, vehicles, animals, flowers, trees, plants, and miniature images of people and objects
    •  more common in Charles Bonnet syndrome
  • simple hallucinations (also described as elementary or nonformed)
    •  feature photopsia (light flashes), lines or patterns, and branching patterns
    •  uncommon in Charles Bonnet syndrome
•  Charles Bonnet plus syndrome – rare condition characterized by visual and auditory hallucinations in patients with visual and auditory impairments and without psychiatric or cognitive conditions⁽²⁾

Epidemiology

Who Is Most Affected

•  older adults (> 70 years old) with visual impairment^(1,2)

Incidence/Prevalence

•  reported prevalence of Charles Bonnet syndrome (CBS) varies greatly^(1,3)
• high variance due to lack of consistent diagnostic criteria, reluctance of patients to report symptoms, and different ascertainment populations^(1,3)
  •  < 1%-30% of persons overall
  •  complex hallucinations reported in 11%-15% of patients with visual impairments
• CBS in 0.47% of patients evaluated in ophthalmology unit in Spain (including 15% of patients with low vision)
  •  based on cross-sectional study
  •  2,502 patients were evaluated in an outpatient ophthalmology unit in Madrid, Spain with comprehensive eye exams and asked about visual hallucinations (VHs)
  •  patients with VHs were referred to multidisciplinary ophthalmology/neurology/psychiatry unit
  • CBS
    •  diagnosed in patients with VHs if other conditions that could induce VHs were ruled out
    •  CBS diagnosed in 12 patients (0.47% of all patients) including 15% of 80 patients with low vision
  •  Reference – Eur J Ophthalmol 2014 Nov-Dec;24(6):960
• visual hallucinations in 18.8% of patients > 40 years old in Canada with eye disease and some vision loss
  •  based on cross-sectional study
  •  2,565 patients > 40 years old with eye disease and some vision loss attending a vision rehabilitation clinic in Canada between July and December 2013 for the first time were asked about VHs (people, animals, patterns, or shapes that they knew were not there)
  •  61% of patients had age-related macular degeneration (AMD), 12% had glaucoma, 7% had diabetic retinopathy, and 20% had other eye disease
  •  psychiatric and cognitive conditions, or history of these conditions, not evaluated
  • VHs reported in 18.8% of patients, including in
    •  19.9% with AMD
    •  18.7% with glaucoma
    •  17.3% with diabetic retinopathy
    •  16.2% with other eye disease
  •  Reference – Can J Ophthalmol 2016 Feb;51(1):3
• CBS in 12% of adults in the Netherlands with eye disease and visual impairment; most did not report their hallucinations to their doctor
  •  based on cross-sectional study
  •  505 adults in the Netherlands with an ophthalmic condition and visual impairment were assessed for complex visual hallucinations
  •  60 patients (12%) aged 46-98 years were diagnosed with CBS (mean age at onset 72 years)
  • CBS defined as having all of the following
    •  ≥ 1 complex visual hallucination within the past 4 weeks
    •  hallucination did not include nonvisual sensory modalities
    •  period between first and last hallucination was ≥ 4 weeks
    •  patient had at least partial insight that the hallucinations were not real
    •  patient did not have any delusions
  • 44 patients with CBS (73%) did not report their hallucinations to doctors
    •  15 patients feared that they would not be taken seriously by their doctor or that they would be labeled “insane”
    •  20 patients thought hallucinations were not an appropriate reason to consult a doctor
    •  9 patients offered no explanation
  •  17 (28%) stated they suffered from their hallucinations and hoped they would go away
  •  Reference – Lancet 1996 Mar 23;347(9004):794
• CBS in 8.3% of patients in the Netherlands with neovascular age-related macular degeneration
  •  based on cross-sectional study
  • 300 patients (median age 80 years) with neovascular age-related macular degeneration in the Netherlands who were treated with ranibizumab were evaluated for Charles Bonnet syndrome during follow-up consultations
    •  all patients were asked “some patients, with similar eye problems as you, report seeing things which are not really there, or which other people do not see; have you experienced this?”
    •  Charles Bonnet syndrome ruled out (for this study) if history of psychiatric or neurological conditions, or if hallucinations were “elementary” (such as floaters or flashes of light)
  •  25 patients (8.3%) responded yes and were classified as having CBS
  • among patients with CBS
    •  16 patients (64%) reported having told someone about their hallucinations
    •  9 patients (36%) reported keeping their hallucinations secret
  •  Reference – Acta Ophthalmol 2012 Aug;90(5):476full-text
• CBS in 6.4% of adults in Turkey with retinal disease
  •  based on cross-sectional study
  • 264 patients in Turkey (mean age 72 years) with retinal disease and best-corrected visual acuity (BCVA) ≤ 20/40 in the better-seeing eye were evaluated for CBS
    •  all patients were asked about visual hallucinations; all patients reporting yes were further evaluated
    •  patients excluded from having CBS if hallucination described as floaters or light flashes, cognitive impairment (Mini-Mental State Exam score < 18 points), current neurological or psychiatric disease, use of antipsychotics or potentially hallucinogenic drugs, or severe metabolic condition
  •  17 patients (6.4%) were diagnosed with CBS
  • among patients with CBS
    •  14 patients had complex visual hallucinations and 3 patients had noncomplex visual hallucinations
    •  retinal diseases included age-related macular degeneration in 12 patients, diabetic retinopathy in 2 patients, bilateral rhegmatogenous retinal detachment in 1 patient, degenerative myopia in 1 patient, and bilateral neovascular glaucoma in 1 patient
  •  Reference – Ophthalmologica 2016;236(1):48

Risk Factors

•  loss of visual acuity, particularly binocular loss^(1,2,3)
• ophthalmologic conditions that may lead to vision loss^(1,2,3)
  •  see Causes section for specific examples
  •  higher prevalence in older patients may be due to higher prevalence of ophthalmologic conditions in these patients
• not living alone, greater vision loss, and female sex associated with increased risk of having visual hallucinations among patients > 40 years old with eye disease and some vision loss
  •  based on cross-sectional study
  •  2,565 patients > 40 years old with eye disease and some vision loss attending a vision rehabilitation clinic in Canada for the first time were asked about visual hallucinations (VHs) (people, animals, patterns, or shapes that they knew were not there)
  •  61% of patients had age-related macular degeneration (AMD), 12% had glaucoma, 7% had diabetic retinopathy, and 20% had other eye disease
  •  psychiatric and cognitive conditions, or history of these conditions, not evaluated
  •  VHs reported in 18.8% of patients
  • factors associated with increased risk of VHs include
    •  not living alone (adjusted odds ratio [OR] 1.54, 95% CI 1.19-1.98)
    •  vision loss worse than 20/69 acuity and 20-degree visual field cone (adjusted OR 1.49, 95% CI 1.19-1.88)
    •  female sex (adjusted OR 1.32, 95% CI 1.06-1.64)
  •  age and type of eye disease not associated with altered risk of VHs
  •  Reference – Can J Ophthalmol 2016 Feb;51(1):3
• lower visual acuity in best-seeing eye and larger area of geographic atrophy each associated with increased risk of having Charles Bonnet syndrome in patients with neovascular age-related macular degeneration
  •  based on cross-sectional study
  • 300 patients (median age 80 years) with neovascular age-related macular degeneration in the Netherlands who were treated with ranibizumab were evaluated for Charles Bonnet syndrome during follow-up consultations
    •  all patients were asked “some patients, with similar eye problems as you, report seeing things which are not really there, or which other people do not see; have you experienced this?”
    •  Charles Bonnet syndrome ruled out (for this study) if history of psychiatric or neurological conditions, or if hallucinations were “elementary” (such as floaters or flashes of light)
  •  25 patients (8.3%) were classified as having Charles Bonnet syndrome
  • comparing patients with vs. without Charles Bonnet syndrome
    •  median visual acuity in best seeing eye 0.45 vs. 0.5 (p = 0.048)
    •  median area of geographic atrophy (areas with no autofluorescence) 2 mm² vs. 0.3 mm² (p = 0.002)
    •  median lesion size (total area with increased autofluorescence) 14.2 mm² vs. 16.2 mm² (not significant)
  •  Reference – Acta Ophthalmol 2012 Aug;90(5):476full-text

Etiology and Pathogenesis

Causes

• Charles Bonnet syndrome may be caused by lesions at any level of the visual pathway including^(2,3)
  •  retina
  •  optic nerve, chiasm, or tract
  •  lateral geniculate nucleus in thalamus
  •  optic radiations
  •  primary visual cortex (thought to be responsible for simple visual hallucinations)
  •  secondary and association visual cortices (thought to be responsible for complex visual hallucinations)
• ophthalmologic diseases that lead to vision loss
  • examples include^(1,2,3)
    • macular degeneration
    • glaucoma
    • cataracts
    •  central retinal artery occlusion
    •  Lebers hereditary optic neuropathy
    •  losing an eye
    • optic neuritis
    • diabetic retinopathy
  • examples in younger patients include⁽²⁾
    •  cone-rod dystrophy
    •  congenital total blindness
    •  optic glioma with extension along optic radiation
•  Charles Bonnet syndrome has also been reported in patient without vision impairment or optic nerve atrophy who had a transsphenoidal adenomectomy for a pituitary macroadenoma; hallucinations occurred when eyes were closed⁽¹⁾
•  visual hallucinations have also been reported to begin after treating underlying condition, possibly due to change in visual acuity rather than correction of visual acuity⁽³⁾

Pathogenesis

• deafferentation theory is the most widely accepted theory of the pathophysiology underlying Charles Bonnet syndrome^(2,3)
  •  reduced visual input due to visual impairments leads to increased spontaneous activity in visual cortices (mostly in ventral occipital lobe)
  •  spontaneous activity in visual cortices manifests as visual hallucinations
  •  plasticity may strengthen neural representations of hallucinations, allowing them to be elicited by weak visual input
• other possible mechanisms include⁽³⁾
  • release phenomenon (similar to deafferentation theory)
    •  reduced visual input (caused by lesions along visual pathway) interferes with normal circuitry responsible for inhibiting activity in visual association cortices
    •  lack of inhibition causes inappropriate excitation of visual cortices and results in “release” of visual hallucinations
    •  visual hallucinations are thought to be subconscious images released to the conscious
  • irritative theory
    •  diffuse irritative lesions in migraines and seizures send abnormal input to visual association cortices
    •  visual association cortices then generate excitatory discharges, which are transmitted to occipital and temporal lobes where they are interpreted as visual hallucinations

History and Physical

History

Chief Concern (CC)

•  visual hallucinations, typically complex and usually not distressing, that the patient knows are not real ^(1,2,3)

History of Present Illness (HPI)

• ask patients with low vision about presence of visual hallucinations
  •  many patients are reluctant to report hallucinations⁽³⁾
  • example phrasing:
    •  “We had a patient here the other day that had a similar problem with their eyes to yourself. The condition made it difficult to see things and they also noticed that they could see things that were really not there or that other people didn’t see. Has this ever happened to you?” ⁽³⁾
    •  “Some patients, with similar eye problems as you, report seeing things which are not really there, or which other people do not see; have you experienced this?” (Acta Ophthalmol 2012 Aug;90(5):476full-text)
•  when asking patient about visual hallucinations, reassure patient that hallucinations do not necessarily indicate psychiatric or progressive neurological disorders⁽³⁾
• ask if patient knows that visual hallucinations are not real, or if sometimes it’s hard to tell
  •  patients with Charles Bonnet syndrome (CBS) usually have retained insight into unreal nature of visual hallucinations and being aware that they do not represent real stimuli^(1,2,3)
  •  CBS is characterized by a lack of psychiatric or cognitive impairment, even during hallucinations⁽³⁾
  •  in some reported cases, patient may initially be confused by hallucinations and think that they are real, but ultimately realize it is not (J Clin Neurosci 2007 Aug;14(8):709)
•  ask when hallucinations started; CBS typically follows loss of visual acuity or other visual impairment^(1,2,3)
•  ask if hallucinations are always visual or if they incorporate auditory or other sensory modalities (nonvisual hallucinations are rare in CBS)^(1,2,3)
• ask if visual hallucinations are pleasant, neutral, frightening, or otherwise distressing^(1,2,3)
  •  visual hallucinations in CBS are usually not distressing, but they can be, especially when first encountered
  •  hallucinations reported be distressing or eliciting “negative” reactions in around 30% of patients
  •  if patient usually finds them distressing, medications may be considered
• ask if hallucinations are usually somewhat realistic and represent objects and environments, or if they usually consist of abstract lines or patterns^(1,2,3)
  • visual hallucinations in CBS are often complex
    • complex visual hallucinations feature realistic scenes and vivid and complicated images
      •  specific characteristics vary greatly
      •  reported images include people, faces, vehicles, animals, flowers, trees, plants, and miniature images of people and objects
      •  images are often static but can move en bloc or partially with pieces in motion within a static frame
      •  images are usually color but can be black and white
  •  visual hallucinations in CBS may also be simple, featuring photopsia (light flashes), lines or patterns, and branching patterns
• ask about frequency and duration of hallucinations, and if they recur
  •  hallucinations in CBS typically occur daily and last a few minutes, but frequency and duration of episodes can vary greatly⁽¹⁾
  •  hallucinations may be persistent or recurring, including episodes recurring for days or years^(1,3)
• ask if hallucinations tend to occur under specific conditions; reported examples include
  •  in environments with bright light or environments with low light⁽³⁾
  •  while fatigued or while feeling stressed⁽³⁾
  •  during a certain part of the day (such as evenings) (Lancet 1996 Mar 23;347(9004):794)
  •  while inactive, at home, alone, watching television, or sitting in a car (Lancet 1996 Mar 23;347(9004):794)
  •  while using temazepam (Lancet 1996 Mar 23;347(9004):794)
• ask about actions that may stop or reduce risk of visual hallucinations
  • commonly reported examples include ⁽³⁾
    •  blinking or other strategies that “interrupt” visual input
    •  concentrating on something else when hallucination occurs
    •  walking toward or talking to hallucination
  • other examples include
    •  looking or walking away from hallucination
    •  closing eyes
    •  swiftly moving eyes
    •  hitting or shouting at hallucination
    • Reference – Lancet 1996 Mar 23;347(9004):794
• 28% of patients with Charles Bonnet syndrome reported to suffer from emotional distress due to hallucinations
  •  based on cross-sectional study
  •  505 adults with an ophthalmic condition and visual impairment were assessed for complex visual hallucinations
  • Charles Bonnet syndrome diagnosed if all of the following were met
    •  ≥ 1 complex visual hallucination within the past 4 weeks
    •  hallucination did not include nonvisual sensory modalities
    •  hallucinations occurring for ≥ 4 weeks (or more than 1 month between first and last hallucination)
    •  patient had at least partial insight that the hallucination was not real
    •  patient did not have delusions
  • 60 patients (12%) were diagnosed with Charles Bonnet syndrome
    •  mean age at syndrome onset 72 years
    •  duration of syndrome ranged from 1 month to 30 years
    •  frequency of hallucinations ranged from several times daily to twice yearly
  •  17 patients (28%) “suffered” from the hallucinations and hoped the hallucinations would disappear
  •  6 patients (10%) considered taking medications to alleviated distress caused by hallucinations
  • immediate emotional impact of hallucinations
    •  “negative” in 19 patients (32%) (anxiety in 14 patients and irritation in 5)
    •  mixed emotions in 11 patients (18%)
    •  neutral emotional response in 22 patients (37%)
    •  joy/amusement in 8 patients (13%)
  •  Reference – Lancet 1996 Mar 23;347(9004):794

Medication History

•  ask about medication use, such as brimonidine tartrate (alpha-2 agonist)⁽³⁾

Past Medical History (PMH)

• ask about current or past psychiatric or neurological conditions^(1,2,3)
  •  CBS is characterized by a lack of psychiatric and cognitive impairments
  •  psychiatric or neurological conditions suggest other causes of visual hallucinations (refer the below Differential Diagnosis section for examples)
• ask about current or history of ophthalmologic conditions^(1,2,3)
  •  visual impairment typically precedes onset of CBS
  • examples of ophthalmologic conditions in patients with CBS include
    • macular degeneration
    • glaucoma
    • cataracts
    •  central retinal artery occlusion
    •  Lebers hereditary optic neuropathy
    •  losing an eye
    • optic neuritis
    • diabetic retinopathy
• ask about other conditions that may lead to hallucinations, such as
  •  narcolepsy-cataplexy syndrome, and other disorders resulting in sleep deprivation
  •  poor nutrition, specifically food deprivation and vitamin deficiencies
  •  dehydration
  •  see Differential Diagnosis section for other conditions that may lead to hallucinations

Family History (FH)

•  ask about familial history of hemiplegic migraine or migraine coma (suggests hallucinations caused by migraine) (J Clin Neurosci 2007 Aug;14(8):709)
•  ask about familial history of Lebers hereditary optic neuropathy⁽²⁾

Social History (SH)

•  ask about alcohol and illicit drug use (such as lysergic acid diethylamide [LSD], phencyclidine [PCP], cocaine, and amphetamines)⁽³⁾

Physical

HEENT

• perform ophthalmological exam to assess for^(1,2,3)
  •  visual impairments such as reduced visual acuity or scotoma
  • signs suggestive of underlying ophthalmologic conditions including
    • macular degeneration
    • glaucoma
    • cataracts
    •  central retinal artery occlusion
    •  Lebers hereditary optic neuropathy
    • optic neuritis/neuropathy
    • diabetic retinopathy
•  check head and neck for bruits (might suggest carotid stenosis and risk for central retinal artery occlusion [CRAO])

Neuro

• perform neurological exam to assess for^(1,2,3)
  •  impairments including altered consciousness and cognitive defects/dementia
  •  signs of neurological conditions (see Differential Diagnosis section for examples of neurological conditions that may lead to hallucinations)
•  Charles Bonnet syndrome is characterized by a lack of psychiatric and cognitive impairments^(1,2,3)

Diagnosis

Making the Diagnosis

•  suspect Charles Bonnet syndrome (CBS) in patients with visual hallucinations, lack of psychiatric and cognitive impairments, and insight that the hallucinations are not real^(1,2,3)
•  rule out alternate causes of hallucinations^(1,2,3)
•  widely accepted precise diagnostic criteria not established^(1,2,3)

Differential Diagnosis

• targeted line of questioning typically sufficient to rule out alternative causes of hallucinations⁽³⁾
• characteristics that may help distinguish hallucinations of Charles Bonnet syndrome from hallucinations due to other causes include^(1,2,3)
  •  lack of nonvisual sensory modalities (CBS typically involves only visual hallucinations)
  •  lack of psychiatric and cognitive impairments
  •  insight that the hallucinations are not real
• neurological conditions that may have associated visual hallucinations^(2,3)
  • Alzheimer dementia and other types of dementia
  • Lewy body dementia
  •  cognitive impairment
  •  aneurysm
  •  brain infarction, particularly in the occipital lobe; may be accompanied by other symptoms of stroke
  • brain tumor (primary or secondary)
  •  cerebral vasculopathy
  • Creutzfeldt-Jakob disease
  •  delirium and other confusional states
  • epilepsy and other seizure disorders – visual hallucinations are generally brief, simple, and associated with other manifestations of the seizure such as signs on electroencephalogram (EEG)
  • head trauma
  • migraine – preheadache aura may lead to simple visual hallucinations, but complex visual hallucinations are rare
  • multiple sclerosis (MS) – hallucinations may be accompanied by cognitive impairment, but may also be due to MS-mediated optic neuritis
  • Parkinson disease with or without dementia
    •  visual hallucinations can occur after long-term exposure to dopaminergic therapy (such as 10 years after Levodopa therapy)
    •  hallucinations typically occur during evening or night, are associated with vivid dreams and changes in arousal, and are brief in duration (few minutes long)
    •  insight may be retained depending on degree of cognitive impairment
  • peduncular hallucinosis
    •  complex visual hallucinations occurring within a few days after infarct to midbrain and/or thalamus, which may be associated with other central nervous system pathologies
    •  hallucinations may include tactile and auditory components and last a few minutes to several hours
    •  patients maintain insight that hallucinations are not real
  • posterior reversible encephalopathy syndrome (PRES)
• psychiatric conditions^(2,3)
  • acute psychoses
    •  hallucinations often involve nonvisual sensory modalities
    • postpartum psychosis typically involves hallucinations or delusions involving the infant
  • bipolar disorder
  •  delirium
  • depression
  • schizophrenia
    •  hallucinations are typically auditory, but visual hallucinations can also occur
    •  hallucinations may also involve personal experiences, have deteriorating clarity, and occur during waking hours or other times of increased arousal
    •  patient likely to have delusions, thought disorders, and paranoia
• narcolepsy – visual hallucinations may occur while falling asleep or awakening, are often disturbing, and may be dream-like and vivid^(2,3)
•  sleep deprivation⁽³⁾
• infections^(2,3)
  •  encephalitis
  • meningitis
• alcohol or illicit drug use (such as lysergic acid diethylamide [LSD], phencyclidine [PCP], cocaine, and amphetamines)^(2,3)
  •  patients may retain insight that hallucinations are not real
  •  visual hallucinations may begin as visual distortions or have other simple features, and then progress to complex hallucinations
  •  stimulant use may lead to auditory or tactile hallucinations
•  metabolic disorders such as metabolic encephalopathy^(2,3)
•  starvation⁽³⁾

Testing Overview

• perform diagnostic testing to evaluate for possible ophthalmologic conditions and to rule out alternate causes of visual hallucinations^(2,3)
  •  standard blood tests and urine studies
  •  additional testing including brain imaging may be considered based on clinical suspicion
  •  other than evaluating for ophthalmologic conditions and ruling out alternate causes of hallucinations, brain imaging is not used for diagnosis of Charles Bonnet syndrome

Blood Tests

• perform standard blood tests to rule out other causes of visual hallucinations; testing should include^(2,3)
  •  complete blood count (CBC)
  •  electrolytes
  •  glucose
  •  thyroid, renal, and hepatic function
  •  vitamin B12
  •  folate

Imaging Studies

•  consider cerebral magnetic resonance imaging (MRI) or computed tomography (CT) to assess orbits, optic nerves, or other visual system structures to help determine cause of visual hallucinations^(2,3)
• other imaging modalities remain experimental for this condition
  • specific ventral extrastriate areas associated with specific characteristics of spontaneous hallucinations in patients with Charles Bonnet syndrome, and ventral extrastriate areas in these patients may have increased functional magnetic resonance imaging (fMRI) signals in response to external stimuli compared to participants without history of hallucinations
    •  based on small case-control study without statistical comparisons between groups
    •  8 patients with Charles Bonnet syndrome and 5 control patients matched for age, visual acuity, and visual field defect and without history of hallucinations had fMRI assessments
    • in experiment 1
      •  patients with CBS instructed to signal the onset and offset of hallucinations during a 5-minute fMRI scan in a room with dimmed lighting
      •  4 patients reported having hallucinations
      • ventral extrastriate areas had fMRI activity associated with specific hallucination characteristics, including
        •  posterior fusiform gyrus with colored hallucinations
        •  behind and above posterior fusiform gyrus with black-and-white hallucinations
        •  right middle fusiform gyrus with hallucinations of objects
        •  left middle fusiform gyrus with a hallucination of a face
        •  around the collateral sulcus with hallucinations of textures
    • in experiment 2
      •  all participants viewed nonspecific visual stimuli (“noise” for 30 seconds alternating with black screen for 30 seconds over 5 minutes) during fMRI scan
      •  compared to control participants, patients with CBS had greater mean fMRI signals in ventral extrastriate areas over the 5-minute experiment (p < 0.025); difference reported to be due to signals elicited during black screen presentations
    •  Reference – Nat Neurosci 1998 Dec;1(8):738
  •  hyperperfusion on ¹²³I-IMP single photon emission computed tomography (SPECT) with some asymmetry in lateral temporal cortex, striatum, and thalamus reported in patients with CBS
    •  based on case series
    • 5 patients with CBS (onset at mean age 71 years) were evaluated with SPECT using ¹²³I-IMP during visual hallucinations
      •  SPECT findings were assessed in paired frontal, lateral temporal, mesial temporal, parietal, occipital, striatal, and thalamic regions
      •  all patients had T1- and T2-weighted MRI before SPECT studies
    •  all patients showed hyperperfusion with some asymmetry in the lateral temporal cortex, striatum, and thalamus
    •  MRI showed mild-to-moderate brain atrophy in the occipital lobes in 3 patients, of whom 1 had mild atrophy in temporal lobes, 1 had mild atrophy in parietal lobes, and 1 had mild atrophy in both
    •  Reference – Psychiatry Clin Neurosci 2000 Apr;54(2):157full-text

Other Diagnostic Testing

• electroencephalography (EEG)
  •  consider EEG to investigate suspected Charles Bonnet syndrome (CBS) and to rule out other causes of hallucinations⁽²⁾
  • EEG-detected periodic lateralized epileptiform discharges associated with focal ictal discharge associated with visual hallucinations in case report of 65-year-old woman
    •  patient had intraparenchymal hemorrhage 4 months previous and was admitted to hospital for recent gait disturbances and other neurological symptom exacerbations, including visual hallucinations
    •  ictal patterns and hallucinations resolved within 6 days after adjusting antiseizure medication
    •  Reference – Epilepsy Behav 2010 May;18(1-2):119

Management

Management Overview

•  no standard treatment exists for Charles Bonnet syndrome (CBS)^(1,2,3)
• reassure patient that CBS⁽³⁾
  •  is benign
  •  is not uncommon after onset of vision impairment
  •  is not a symptom of and does not progress to dementia or mental instability
•  for patients with vision impairment, consider corrective steps as appropriate, such as corrective lenses and low-vision rehabilitation
•  if present, treat underlying ophthalmologic condition, including with surgery if appropriate
•  if visual hallucinations are associated with specific environmental conditions, consider steps that may change the environment or patient’s perceptions such as increasing light levels
•  consider other actions that have been reported to stop hallucinations, such as rapid blinking and concentrating on something else
•  if visual hallucinations are continuous and distressing, consider medications that have been reported to reduce symptoms and hallucinations such as antipsychotics, antiseizure medications, and selective serotonin reuptake inhibitors (SSRIs)

Medications

• if visual hallucinations are continuous, disturbing, or otherwise distressing, consider medications that have been reported to reduce hallucinations, but evidence limited to case reports and small case series^(1,2,3)
  • antipsychotics
    •  clozapine
    •  haloperidol
    •  melperone
    •  olanzapine
    •  quetiapine
    •  risperidone
  • antiseizure medications
    •  carbamazepine
    •  clonazepam
    •  gabapentin
    •  phenytoin
    •  valproate (but note risk of congenital malformations, FDA DailyMed 2018 Jan)
  • SSRIs
    •  cisapride
    •  ondansetron
    •  venlafaxine
  •  cholinesterase inhibitors
  •  diazepam

Surgery and Procedures

• surgical and other procedures treating ophthalmologic conditions may reduce or eliminate accompanying visual hallucinations; examples include^(1,2,3)
  •  cataract extraction
  •  laser photocoagulation for subretinal hemorrhage or diabetic retinopathy
  •  laser and surgical procedures for primary open-angle glaucoma, but evidence evaluating visual acuity and other clinical outcomes is limited
  •  photodynamic therapy and other procedures for age-related macular degeneration
• transcranial direct current stimulation (tDCS) using cathodal stimulation to visual cortex might reduce frequency of visual hallucinations in patients with Charles Bonnet syndrome caused by eye disease (level 2 [mid-level] evidence)
  •  based on small randomized crossover trial
  • 17 patients with Charles Bonnet syndrome secondary to visual impairment due to eye disease and with recurrent visual hallucinations (≥ 3 times/week) were randomized to tDCS using cathodal stimulation to visual cortex vs. placebo on days 1-4 and then switched to other treatment following 4-week washout period
    • tDCS: active stimulation (current density 0.29 milliamperes/cm² ) was delivered in 4 sequential 5-minute periods separated by 2-minute intervals on day 1, and as 6 sequential 5-minute periods separated by 2-minute intervals on days 2-4
    • placebo stimulation: direct current was applied at same intensity as active stimulation for first and last 20 seconds of procedure to generate scalp sensations without neuromodulatory effects
  • all patients had Mini Mental State Exam (MMSE-Blind) score ≥ 24 points
  • exclusion criteria included Geriatric Depression Scale score > 10 points, history of moderate-to-severe cerebrovascular disease, and epilepsy
  • primary outcomes were frequency and duration of visual hallucinations on day 5 assessed using
    • North-East Visual Hallucination Interview (NEVHI)
      • for frequency (score range 1-8 points, with higher scores indicating higher frequency)
      • for duration (score range 1-4 points, with higher scores indicating longer duration)
    • Neuropsychiatric Inventory (NPI) hallucination frequency subscale (score range 1-4 points, with higher scores indicating higher frequency)
  • 16 patients (94%) (mean age 78 years, 63% female) completed trial and were included in analysis
  • at baseline
    • 69% had age-related macular degeneration
    • median NEVHI frequency score was 5 points (every few hours)
  • comparing tDCS vs. placebo stimulation on day 5
    • median NEVHI frequency score 4.5 points vs. 5 points (p = 0.007)
    • median NEVHI duration score 2 points vs. 2 points (not significant)
    • median NPI hallucination frequency score 4 points vs. 4 points (p = 0.08)
    • adverse events
      • headache in 43.8% vs. 6.3% (p = 0.014, NNH 2)
      • tingling sensation from electrodes in 75% vs. 68.8% (no p value reported)
  • no significant between-group differences in visual acuity and contrast sensitivity
  • Reference – Ophthalmology 2022 Dec;129(12):1368
•  see Causes for additional possible causes of vision impairment that may lead to Charles Bonnet syndrome

Consultation and Referral

•  refer to psychologist or psychiatrist for formal evaluation of cognitive function to rule out other causes of visual hallucinations⁽³⁾
• randomized trial evaluating addition of psychiatric evaluation to ophthalmologist consultation in 34 adults ≥ 55 years old with Charles Bonnet syndrome can be found in BMJ Open Ophthalmol 2021;6(1):e000463full-text

Other Management

• educate patient and family about Charles Bonnet syndrome⁽³⁾
  • focus on reassuring patient that syndrome
    •  is benign
    •  is not uncommon after onset of vision impairment
    •  is not a symptom of and does not progress to dementia or mental instability
  •  encourage patient to join support group for individuals with ocular pathologies who experience similar phenomena
  •  see Patient information section for handouts and links
• for patients with vision impairments, consider corrective steps as appropriate, such as
  •  corrective glasses or contacts⁽³⁾
  • low vision rehabilitation strategies⁽³⁾
    •  review of low vision rehabilitation can be found in Front Syst Neurosci 2017;11:82full-text
  •  strategies that increase sharpness and reduce blur and glare (Clin Exp Optom 2004 May;87(3):149PDF)
  •  for patient with peripheral field loss due to glaucoma, visual hallucinations (VHs) reported to disappear over time after wearing glasses full time, adding tinted shields in brightly lit environments, and using nightlights in bedroom and bathroom (Clin Exp Optom 2004 May;87(3):149PDF)
  •  for patient with hemianopia, VHs reported to disappear with use of Fresnel/ground-in prism (Clin Exp Optom 2004 May;87(3):149PDF)
• if VHs are associated with specific environmental conditions, consider steps that may change environment or patient’s perceptions, such as
  •  increasing light levels if VHs associated with dimly lit environments⁽³⁾
  •  blinking or closing eyes if VHs associated with brightly lit environments⁽³⁾
  •  minimizing emotional states or exposure to conditions associated with VHs (see examples in History of present illness section)
• consider other actions reported to temporarily stop or reduce risk of VHs
  •  blinking or other strategies that “interrupt” visual input⁽³⁾
  •  concentrating on something else when VHs occur⁽³⁾
  •  strengthening social networks (for patients who report having poor social interaction)⁽³⁾
  •  walking toward or talking to VH⁽³⁾
  •  looking or walking away from VH (Lancet 1996 Mar 23;347(9004):794)
  •  closing eyes (Lancet 1996 Mar 23;347(9004):794)
  •  swiftly moving eyes (Lancet 1996 Mar 23;347(9004):794)
•  for patient who experienced VHs while watching television, VHs reported to disappear with use of monocular telescope plus eyepatch (Clin Exp Optom 2004 May;87(3):149PDF)
•  consider other management as appropriate, depending on underlying condition; see Causes section for additional possible causes of vision impairment that may lead to Charles Bonnet syndrome

Complications

•  emotional distress/anxiety^(1,2)

Prognosis

•  recurrent hallucinations may continue for days to years⁽³⁾
•  hallucination episodes may cluster across days or weeks and recurrence following symptom-free interval may occur (J Clin Neurosci 2007 Aug;14(8):709)
• hallucinations have been reported to disappear following
  •  treatment of ophthalmologic disorder^(1,2,3)
  •  progression of visual impairment, including to total blindness (J Clin Neurosci 2007 Aug;14(8):709, Clin Exp Optom 2004 May;87(3):149PDF)
•  attributing Charles Bonnet syndrome to mental illness and not knowing about syndrome before onset are among factors associated with negative overall effect of syndrome on patient’s life
  •  based on cohort study
  • 492 patients with macular disease and Charles Bonnet syndrome (CBS) were evaluated by mail with questionnaire
    •  CBS status determined by question asking if patient has CBS
    •  additional 762 patients with macular disease responded that they did not have CBS; additional 2,746 patients with macular disease did not respond to questionnaire
  • comparing emotional response to hallucination at CBS onset vs. at time of questionnaire (all values estimated from figure)
    •  startle in 25% vs. 7% (p < 0.001)
    •  fright in 15% vs. 2% (p < 0.001)
    •  terrified in 4% vs. 1% (p < 0.001)
    •  curiosity in 37% vs. 27% (p < 0.01)
    •  indifference in 12% vs. 38% (p < 0.001)
  • overall effect of CBS on life reported to be
    •  “very negative” in 8%
    •  “fairly negative” in 25%
    •  negligible (“no real effect”) in 60%
    •  “fairly pleasant” in 6%
    •  “very pleasant” in 1%
  • factors associated with very or fairly negative overall effect include
    •  longer duration hallucinations (p < 0.0001)
    •  more frequent hallucinations (p = 0.0001)
    •  fear-inducing hallucinations at CBS onset (p < 0.0001)
    •  ≥ 1 daily activity affected (p < 0.0001)
    •  attributing CBS to mental illness (p = 0.01)
    •  lack of knowledge of CBS onset (p = 0.04)
  •  factors not associated with very or fairly negative overall effect include sex, wet vs. dry macular disease, CBS duration, hallucination content, attributing CBS to vision impairment, or quality of information about CBS given to patient
  •  Reference – Br J Ophthalmol 2014 Sep;98(9):1236full-text

Prevention

•  not applicable

Screening

• screen for Charles Bonnet syndrome in patients with low vision^(1,2,3)

Guidelines and Resources

Guidelines

•  Royal Australian and New Zealand College of Ophthalmologists (RANZCO) position statement on Charles Bonnet syndrome can be found at RANZCO 2018 November PDF

Review Articles

• reviews can be found in
  • Psychiatr Danub 2018 Jun;30(2):122
  • J Psychiatr Ment Health Nurs 2013 Mar;20(2):169
  • J Clin Neurosci 2007 Aug;14(8):709
  • Surv Ophthalmol 2003 Jan-Feb;48(1):58, commentary can be found in Am J Emerg Med 2013 Mar;31(3):624
• review of pyschological and social factors in Charles Bonnet syndrome can be found in Ther Adv Ophthalmol 2021 Jan-Dec;13:25158414211034715
•  case report of Charles Bonnet syndrome following trans-sphenoidal adenomectomy in patient without optic nerve atrophy can be found in Psychiatry Investig 2016 Sep;13(5):577full-text

MEDLINE Search

•  to search MEDLINE for (Charles Bonnet syndrome) with targeted search (Clinical Queries), click therapy, diagnosis or prognosis

Patient Information

•  handout from National Center for Advancing Translational Sciences
•  handout from NHS Choices

References

1. Boller F, Birnbaum DS, Caputi N. Charles Bonnet Syndrome and Other Hallucinatory Phenomena. Front Neurol Neurosci. 2018;41:117-124.
2. Lerario A, Ciammola A, Poletti B, Girotti F, Silani V. Charles Bonnet syndrome: two case reports and review of the literature. J Neurol. 2013 Apr;260(4):1180-6.
3. Pang L. Hallucinations Experienced by Visually Impaired: Charles Bonnet Syndrome. Optom Vis Sci. 2016 Dec;93(12):1466-1478full-text.

Summary

• Charles Bonnet Syndrome is a vivid, well-formed visual hallucinations in the setting of poor vision occurring in mentally healthy, most often elderly, individuals.
• Severe macular degeneration and glaucoma are common etiologies, but optic nerve damage can also predispose to the disorder.
• Hallucinations are usually of people, animals, or objects, often “Lilliputian,” and perceived as pleasurable by many patients.