Accepted Manuscript

Palinopsia Revamped: A Systematic Review of the Literature

David Gersztenkorn, MD, MS Andrew G. Lee, MD

PII: S0039-6257(14)00128-3

DOI: 10.1016/j.survophthal.2014.06.003

Reference: SOP 6524

To appear in: Survey of Ophthalmology

Received Date: 4 April 2014

Revised Date: 23 June 2014

Accepted Date: 24 June 2014

Please cite this article as: Gersztenkorn D, Lee AG, Palinopsia Revamped: A Systematic Review of theLiterature, Survey of Ophthalmology (2014), doi: 10.1016/j.survophthal.2014.06.003.

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Palinopsia Revamped: A Systematic Review of the Literature

David Gersztenkorn, MD, MSa, Andrew G. Lee, MD

b

aCenter for Biomedical Engineering, The University of Texas Medical Branch, Galveston, TX, USA

bDepartment of Ophthalmology, Houston Methodist Hospital, Houston, TX, USA, Department of

Neurology, Houston Methodist Hospital, Houston, TX, USA, Departments of Ophthalmology, Neurology,

and Neurosurgery, Weill Cornell Medical College, Department of Ophthalmology, The University of Texas

Medical Branch, Galveston, TX, USA, Houston, TX, USA, Baylor College of Medicine, Houston, TX, USA,

Department of Ophthalmology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA, The

University of Texas MD Anderson Cancer Center, Houston, TX, USA

Corresponding author: Andrew G. Lee, Department of Ophthalmology, Houston Methodist Hospital,

6560 Fannin St. Suite 450, Houston, TX, 77030

Email address: AGLee@houstonmethodist.org

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Abstract

Palinopsia, the persistence or recurrence of visual images after the stimulus has been removed, is a non-

specific term that describes multiple types of visual symptoms with a wide variety of etiologies. For

example, palinopsia may be the presenting symptom of a potentially life-threatening posterior cortical

lesion, yet it may also be a benign medication side effect. We comprehensively review all published

cases and subdivide palinopsia into two clinically significant categories: illusory palinopsia and

hallucinatory palinopsia.

Key Words: Palinopsia; Visual Perseveration; Cerebral Polyopia; Akinetopsia; Hallucinogen Persisting

Perception Disorder; Persistent Migrainous Aura; Persistent Visual Aura; Positive Spontaneous Visual

Phenomena; Visual Snow; Saccadic Suppression

Abbreviations:

HPPD: Hallucinogen persisting perception disorder

CSD: Cortical spreading depression

AVM: Arteriovenous malformation

PCA: Alzheimer variant posterior cortical atrophy

LGN: Lateral geniculate nucleus

MT/MST: Medial temporal/medial superior temporal area

LSD: Lysergic acid diethylamide

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1. Introduction

Palinopsia (Greek: palin for "again" and opsia for "seeing"), defined by Bender et al as “the

persistence or recurrence of visual images after the stimulus has been removed”17

, encompasses many

different visual symptoms. The heterogeneous group of symptoms cannot be accurately classified as

either visual illusions or visual hallucinations, leading to ambiguity in the nosology of palinopsia and of

related terms such as akinetopsia, illusory visual spread, and cerebral polyopia. Palinopsia is

synonymous with visual perseveration137

.

Kolmel first subdivided palinopsia in 1982 based on the latency between the observation of the

true image and the appearance of the palinoptic image81

. Palinopsia may be described as “immediate”

for a latency up to a few seconds or “delayed” for a latency greater than a few seconds. While this

temporal relationship is important, there is now ample evidence to show that it should not be the

primary factor for categorization.

After thoroughly reviewing the 127 cases of palinopsia in the literature (Appendix), we discuss

its symptomology, etiology, pathophysiology, diagnostic evaluation, prognosis, and treatment. We split

palinopic symptoms into two clinically relevant categories. Hallucinatory palinopsia describes

afterimages that are not usually affected by environmental conditions of light or motion and are long-

lasting, isochromatic, and high resolution. This category of palinopsia represents a dysfunction in visual

memory and is caused by posterior cortical lesions or seizures. Illusory palinopsia describes afterimages

that are unformed, indistinct, or low resolution and are affected by ambient light and motion. This

category of palinopsia represents a dysfunction in visual perception and is a result of migraines,

prescription drugs, illicit drugs, or head trauma.

2. Symptomology

2.1. Physiological afterimages

Palinopsia should be distinguished from physiological afterimages, a common and benign

phenomenon. Physiological afterimages regularly appear after viewing a bright stimulus and shifting

visual focus. These afterimages occur in the same location in the visual field as the original stimulus and

lack clarity. The generation of physiological afterimages relies on the intensity and contrast of the

original stimulus, the time of fixation, and the retinal adaptation state11,17,137

. Physiological afterimages

are almost always the complementary color (negative afterimage) to the original stimulus, but can very

briefly be the same color (positive afterimage) when viewing an exceptionally bright stimulus. A stimulus

consistently produces the same afterimage, which varies in size based on the distance between the

person and the background17

. Physiological afterimages can be seen with either eye open, with both

eyes open, or with both eyes shut, and are often revived by blinking. Physiological afterimages are

thought to derive mainly from photobleaching of the retina24,147

, although newer evidence indicates

contribution from cerebral processes131

.

2.2. Palinopsia subtypes

We describe eight categories of symptoms which are all defined as palinopsia. Notably,

palinoptic images are almost always isochromatic (positive afterimage) to the original stimulus.

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2.2.1. Formed image perseveration

Patients may report a single, stationary object remaining fixed in their visual field. The

perseverated images are realistic, with the same color, resolution, and clarity as the original stimulus.

Some patients even try to reach out and touch the afterimage. The palinopsia usually lasts at least 15

seconds, but can persist for several hours or days. For example, a patient sees a picture of a wasp, and

then an identical copy of the wasp is superimposed on the patient’s field of view for a few hours82

. A

typical complaint is retaining the examiner’s fingers in the field of view (Figure 1a). These afterimages

may occur at the original location of the stimulus or appear elsewhere in the visual field, often in a visual

field deficit. The perseverated images are not affected by the length of fixation or external conditions

such as stimulus intensity, contrast, or color. The palinoptic image may appear immediately after

viewing the original image or be temporally delayed. If delayed, the image will usually appear within a

few minutes. On occasion, the perseverated image is part of an object or multiple objects that are close

together.

2.2.2. Scene perseveration

Patients may describe seeing a previously-viewed, short, and stereotyped action which

continuously replays for several minutes. For example, a patient might view a person running his hand

through his hair, and minutes later, sees the same action-sequence repeated many times35

.The

palinoptic scene usually appears within minutes after the original scene, with the same color and clarity.

Scene perseveration may occur in a visual field deficit or be superimposed on an intact visual field. Our

understanding of visual memory considers a short scene as a unit of memory, similar to an image21, thus

scene perseveration is probably mechanistically related to formed image perseveration.

2.2.3. Categorical incorporation

Palinopsia also refers to a patient seeing an object or feature and then superimposing it onto

comparable objects or people. For example, a patient sees a man with a beard and incorporates the

same beard on every subsequent person viewed104

. Or a person sees the spire of a building and

perceives the spire on the top of other structures154

(Figure 1b). The episodes of categorical

incorporation usually last a few minutes. The perseverated images have the same characteristics as the

original stimulus and are not affected by fixation, light, contrast, or motion. Categorical incorporation

highlights the brain’s use of constructs to process the external world.

2.2.4. Illusory visual spread/patterned visual spread

Illusory visual spread or patterned visual spread is a rare type of palinopsia that describes the

spread of a pattern to other objects in a single field of view. For example, a patient sees a checkered

pattern on a lamp, which then spreads to other objects, such as the floor or a desk. The visual spread is

not influenced by contextual clues, differentiating it from categorical incorporation. Illusory visual

spread was renamed to patterned visual spread for clarity.

2.2.5. Prolonged indistinct afterimage

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After viewing a bright stimulus or a light and then looking away, some patients report seeing a

prolonged afterimage in the same location in the visual field as the original stimulus. The indistinct or

unformed perseverated image or light is typically isochromatic to the original stimulus, but can fade to

different colors over time. For example, after viewing a light-post, a bright outline of the post stays in

one’s visual field for several minutes122

. Stimulus intensity, background contrast, and fixation length

affects the generation and severity of these perseverated images. Photophobia frequently co-exists,

which can hamper a patient’s ability to perform outdoor activities. Afterimages from lights tend to have

a longer duration than the indistinct afterimages from other bright objects. Patients often complain of

trouble with camera flashes, which may stay in their visual field for ten minutes or longer140

. Palinoptic

prolonged light afterimages of the complementary color are differentiated from physiological

afterimages based on afterimage intensity and duration.

2.2.6. Light streaking

Light streaking occurs when relative motion between a person and a light source causes streaks

to appear behind the light, usually persisting for several seconds before fading. This type of palinopsia

commonly occurs with a bright light on a dark background. Difficulty with night driving is a common

complaint, as vision is obscured by multiple streaks from the headlights of oncoming cars1. The streaking

can appear anywhere in the visual field, depending on the location of the light movement.

2.2.7. Visual trailing

Some patients report that an object in motion leaves copies in its wake, colloquially called visual

trailing or ghosting (Figure 1c). The perseverated images left behind the moving object may be discrete

and discontinuous such as in a film reel or in a multiple-exposure photograph, or the afterimages may

be blurred together such as in a long-exposure photograph. Delayed image elimination after motion has

been described as “seeing Neo dodge bullets in the movie, The Matrix”132

. The perseverated images last

a few seconds and are identical in shape and color to the original stimulus, but they are often less

intense. Visual trailing is sometimes more noticeable in the temporal fields. Some patients report that

the afterimages catch-up and integrate with the original stimulus after motion ceases. Most cases

describe visual trails during movement of an object; however there are also reports from the movement

of the observers’ head or eyes66,117

.

2.2.8. Variant image perseveration

There are a few people who report palinopsia with many of the features of formed image

perseveration (Section 2.2.1.), but with some important differences. One variant consists of a formed

perseverated image that is similar to the original but fades after only a couple of seconds. Another

variant consists of a formed afterimage that is black or translucent. These variants usually lack the

realistic clarity of formed image perseveration, and the generation of the palinoptic images is affected

by fixation time, motion, stimulus intensity, or contrast.

2.3. Palinopsia symptom groups

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We divide the subtypes of palinopsia into two symptomatic groups. Illusory palinopsia consists

of prolonged indistinct afterimages, light streaking, visual trailing, and momentary formed image

perseveration. The palinopsia is exposed or exacerbated based on environmental parameters and often

occurs continuously or predictably such as in the morning or during light adaptation. These perseverated

images appear in the same location in the visual field as the original stimulus and are likely due to

sustained awareness of the previously-viewed object. Illusory palinopsia is similar to a visual illusion: the

distorted perception of a real external stimulus.

Hallucinatory palinopsia consists of formed image perseveration, scene perseveration,

categorical incorporation, and patterned visual spread. The perseverated images or scenes can appear

anywhere in the visual field regardless of the location of the original stimulus, have high resolution, and

are typically not reliant on environmental parameters such as contrast, light, and motion. These formed,

high-fidelity afterimages or scenes are likely the projection of an already-encoded visual memory.

Hallucinatory palinopsia is similar to a complex visual hallucination: the creation of a formed visual

stimulus where none exists.

Those who report multiple types of palinopsia usually have all of their symptoms from the same

group, which suggests etiologic and mechanistic similarity. Patients with variant formed image

perseveration have characteristics from both groups, the significance of which will be discussed later

(Section 4.2.).

2.4. Associated symptoms

Patients with both groups of palinopsia often have visual illusions and hallucinations such as

visual snow, micropsia, macropsia, teleopsia, pelopsia, dysmetropsia (“Alice in Wonderland” syndrome),

oscillopsia, phosphenes, and photopsias. Some patients briefly think that the perseverated images are

real, but palinopsia is not associated with delusional ideation or psychosis. Below are terms that are

symptomatically related to palinopsia.

2.4.1. Cerebral polyopia

Cerebral diplopia or polyopia occurs when a patient sees two or more duplicated images

arranged in ordered rows or columns after fixation on an object18,73,153

. The polyopic images occur

monocular bilaterally and binocularly, differentiating it from ocular polyopia. Cerebral polyopia is

sometimes confused with visual trailing, however in cerebral polyopia, the rows or columns of

duplicated images move with the original object, or the polyopic images disappear during motion. In

palinoptic polyopia, movement causes each polyopic image to leave a perseverated image in its wake,

creating hundreds of palinoptic images (entomopia)75,97

.

2.4.2. Akinetopsia

Akinetopsia is defined as a failure to perceive motion, which can occur with or without

palinopsia. Akinetopic palinopsia (visual trailing) is often described as stroboscopic vision. Motion

appears fragmented and afterimages are left at the previous location where the moving object was

observed. Depth perception affects motion perception, and two patients with akinetopic palinopsia had

decreased stereopsis53,94

.

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2.4.3. Visual allesthesia

Visual allesthesia occurs when fixation on an object causes its duplication in the opposite

hemifield. If the patient looks away from the original image and the duplicated image is still retained,

then the patient has visual allesthesia and formed image perseveration palinopsia.

2.4.4. Entoptic phenomena

Entoptic phenomena are the observation of real, physiologic processes within the eye. Examples

include squiggly lines representing white blood cells moving through retinal capillaries or tree-like

outlines representing the retinal vasculature. Entoptic phenomena are the continuous viewing of new

stimuli, different from the persistent or recurrence of a previously viewed stimulus (palinopsia). Entoptic

phenomena may be the result of visual pathway hypersensitivity causing the perception of normally

subthreshold stimuli.

3. Etiology and pathophysiology

Palinopsia has a wide variety of etiologies and mechanisms, which relate to the previously-

defined symptomatic groups.

3.1. Etiology: Post-geniculate cortical lesions

We found 44 cases of palinopsia from posterior visual pathway lesions, and all but three

described hallucinatory palinopsia (formed image perseveration, categorical incorporation, scene

perseveration, patterned visual spread). There were 17 cases of cerebrovascular accidents (CVAs) 10,35,38,57,61,85-87,104,106,111,122,145,146,A

, 26 cases of space-occupying lesions, one case of idiopathic gliosis37

, and

one case of cortical dysplasia113

(Appendix). Of the 26 cases of palinopsia from a space-occupying lesion,

14 were neoplasms17,30,77,82,89,91,104,111,151,153

, five were infectious lesions, five were arteriovenous

malformations (AVMs)45,69,84,122

, and one was an aneurysm17

. Of the infectious causes, there were three

abscesses (in the setting of acute myeloid leukemia116

, Kartagener syndrome98

, and Noonan

syndrome11

), one tuberculoma149

, and one case of neurocysticercosis10

.

Palinopsia, once considered a disorder of the non-dominant parieto-occipital lobe, has since

been shown to occur from lesions in the dominant or non-dominant temporal, parietal, or occipital

lobes. There are 24 reported cases of palinopsia with lesions in the occipital cortex, five in the parietal

cortex, two in the temporal cortex, eight in the occipito-parietal area, five in the occipito-temporal area,

and one in the occipito-parieto-temporal area. There were 35 cases with right-sided pathology, nine

with left-sided pathology, and one lesion was midline. The predominance of right-sided lesions might be

from anatomical or functional differences in visual memory encoding26

. Palinopsia from post-geniculate

cortical lesions is caused by focal cortical hyperactivity, which may be from cortical deafferentation,

epileptic discharges, or cortical irritation.

3.1.1. Pathophysiology: Cortical deafferentation hyperexcitability

Palinopsia commonly occurs in the setting of posterior visual pathway deafferentation causing

homonymous visual field deficits, of which patients are frequently unaware (hemianopic anosagnosia).

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Of the 43 patients with homonymous visual field deficits, 40 (93%) described hallucinatory palinopsia

(Appendix). This palinoptic mechanism is thought to be similar to visual release hallucinations (Charles-

Bonnet Syndrome)37

which are due to neuronal hyperexcitabiity, often from ocular vision loss.

Hallucinatory palinopsia is due to focal cortical hyperexcitability from cortical visual loss. Visual release

hallucinations are distinguished from palinopsia by content (if the formed image or scene actually

occurred). Deafferentation hyperexcitability is a well-studied phenomenon, also seen in neuropathic

pain and phantom limb syndrome. Molecular changes include a presynaptic increase in

neurotransmitter vesicle size and number, increased post-synaptic receptor sensitivity, and alterations

in extracellular neurotransmitter concentrations27

.

3.1.2. Pathophysiology: Epileptic discharges

Palinopsia may occur during a seizure aura, the ictal phase, and post-ictally, with the epileptic

discharges confirmed by electroencephalogram (EEG) 18,50,91,111

. The seizures can originate in the

temporal, parietal, or occipital lobe, depending on the lesion location. The discharge may stay localized

or spread, although there is rarely seizure generalization70,111. Some visual seizures do not have the

commonly associated motor and sensory symptoms, and there are case reports of palinopsia as the only

symptom of the seizure111

. The palinoptic seizure may leave the primary visual pathway unaltered152

or

the patients may report visual field loss related to the seizure, with the palinopsia appearing in the field

deficit85

.

3.1.3. Pathophysiology: Focal cortical irritation

Palinopsia after neurosurgical procedures or cerebrovascular events is attributed, in part, to

focal cortical irritation70,85,154

. Hayashi et al report palinopsia is associated with perilesional

hyperperfusion, which could reflect focal cortical instability and hyperactivity61

.

3.2. Etiology: Metabolic or systemic disease

There are seven case reports of palinopsia in the setting of a metabolic or systemic disease:

three from uncontrolled diabetes causing hyperglycemic seizures25,72,106

, two attributed to transient

ischemic attacks117,140

, one from carnitine deficiency causing secondary seizures80

, and one in Leber

hereditary optic neuropathy (the only report of palinopsia from ocular vision loss)117

. All of these

patients had visual field deficits or seizures, suggesting a similar mechanism to palinopsia caused by

post-geniculate cortical lesions (sections 3.1.1. and 3.1.2.). These patients all reported hallucinatory

palinopsia (Appendix).

3.3. Etiology: Idiopathic seizures

Epileptic discharges are commonly associated with palinopsia, but the seizure is usually

secondary to an easily diagnosable cortical lesion or metabolic disturbance (section 3.1. and 3.2.). There

are six cases of palinopsia from idiopathic seizures17,75,107,115,133,141

, five of which reported hallucinatory

palinopsia (Appendix).

3.4. Etiology: Diffuse cortical pathology

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There are nine cases of palinopsia from diffuse cortical pathology: three from multiple

sclerosis8,71,117

(MS), three from posterior cortical atrophy (PCA) variant of Alzheimer disease33,145

, one

from a primary B cell lymphoma with unremarkable neuroimaging135

, one from Creutzfeld-Jacob disease

(CJD)119, and one from an epileptic ion channel mutation42 (Appendix). The patients with the ion channel

mutation, CJD, and primary B-cell lymphoma had epileptic discharges (section 3.1.2.), and these patients

described hallucinatory palinopsia. All of the patients with multiple sclerosis experienced the black or

translucent variant of formed image perseveration. One patient developed unilateral, monocular

palinopsia after a bout of optic neuritis, perhaps indicating a pre-chiasmatic lesion117

. To note, one

patient with MS had focal white matter enhancement but still was included in the diffuse cortical

pathology group8. The PCA cases will be discussed later (Section 5.3.3.).

3.4.1. Pathophysiology: Demyelination

MS causes inflammatory demyelination in the CNS, affecting the anterior and posterior visual

pathways. Demyelination is associated with increased inflammatory cytokines and synaptic

hyperexcitability123.

3.5. Etiology: Drug-induced

3.5.1. Illicit drugs

There are 14 cases of palinopsia attributed to the intake of illicit drugs, all of which reported

illusory palinopsia1,9,53,76,92,94,102,140

(Appendix). One case described both types of palinopsia. After taking

hallucinogens, as many as 50% of people experience “flashbacks”, a spontaneous and often transitory

feeling of being under the influence of the drug which occurs any time after drug ingestion. If these

experiences are prolonged, pervasive, and recurrent, it is known as hallucinogen persisting perception

disorder (HPPD). Lysergic acid diethylamide (LSD ) is the most common cause of HPPD, which occurs in

about 5% of past users. Psylocibin (psychedelic mushrooms), 3,4 methylenedioxy-N-

methylamphetamine (MDMA or ecstasy), and cannabis (marijuana) have also been implicated41

. The

visual symptoms of HPPD include illusory palinopsia (light streaking, visual trailing, prolonged indistinct

afterimages, prolonged light afterimages, momentary formed image perseveration), dysmetropsia,

oscillopsia, visual snow, halos, entopic phenomena, and photopsias2,14

.

HPPD is more commonly and thoroughly described in the psychiatric literature and palinoptic

symptoms are often not defined as palinopsia. Patients are often reluctant to admit drug use, and

palinopsia from HPPD is likely relatively common. The relationship between the number and strength of

hallucinogen doses and HPPD is not clear, but there are reports of HPPD after minimal hallucinogen use,

sometimes after just one dose2,59,94

.

3.5.2. Prescription drugs

There are 27 case reports of palinopsia from prescription drugs. All except two of the patients

described illusory palinopsia, which would often co-exist with other visual illusions and unformed

hallucinations (Appendix). These symptoms typically occur during drug initiation or dose increase and

resolve after drug discontinuation. There are four published cases solely from trazodone along with nine

unpublished cases that occurred during clinical trials1,66

. There are eight cases from

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nefazodone48,65,67,83,108,127

, which is rarely used because of serious adverse effects. There is one case of

palinopsia from mirtazepine68

, two cases from topiramate46,49

, and one case from zosuquidar124

. There

are three cases of palinopsia from risperidone5, which caused a relapse of HPPD. There are three cases

of clomiphene-induced palinopsia along with more complaints of “visual disturbances” in FDA reports120.

Clomiphene caused permanent symptoms. There are also three cases from a combination of the

aforementioned drugs46,88,132

. There are single reports of palinopsia from maprotiline and interleukin-2,

although there was a questionable link between the symptoms and the drugs51,64

.

3.5.3. Pathophysiology: Diffuse neurotransmitter and neurotransmitter receptor alterations

The illusory palinopsia induced by drugs is mainly caused by antidepressants and HPPD after

LSD, both of which act primarily on the serotonergic system. The main target of LSD is the 5HT2a

receptor, and Abraham et al found that HPPD is associated with 5HT2a receptor excitotoxicity3.

Additionally, nefazodone and trazodone are 5HT2a receptor antagonists. Le Grand et al found that

serotonin depletion leads to cortical hyperexcitability90

.

Drugs such as topiramate or clomiphene also cause palinopsia but are not considered to be

strongly associated with the serotonergic system. The symptoms may be related to a disruption in

GABAnergic transmission, which is facilitated by the 5HT2a receptor129

. Topiramate is also known to

modulate cortical excitability12

, and Abraham et al found cortical disinhibition in HPPD4. Regardless, the

neuropharmacology of the visual system is exceedingly complex and neurotransmitter profiles are

largely unstudied.

Illusory palinopsia is strikingly dependent on external light or the motion of an object. Light and

motion perception are dynamic operations involving processing and feedback from structures

throughout the central nervous system: retina, lateral geniculate nucleus (LGN), V1-V5, superior

colliculus, frontal eye fields, Edinger-Westphal nucleus, etc. We approach illusory palinopsia by

considering the impact of diffuse neuronal excitability alterations on physiological mechanisms for light

and motion perception.

3.5.3.1. Dysfunction in light perception

Light perception depends on the external parameters of the stimulus as well as internal

conditions such as neuronal depolarization sensitivity, retinal adaptation state, and cortical adaptation

state. Light contrast and intensity is mostly processed in V1, although processing and feedback from

many other structures throughout the visual pathway affect light perception55

. For example, retinal

ganglion cells can merge neural signals to increase light sensitivity and alter the perception of the

signal44

. Olsen et al show that layer 6 of V1, an area with many corticothalamic neurons, is especially

important in light and contrast perception114, highlighting the significance of the feedback loops.

Dysregulated cortico-thalamo-retinal feedback could cause failed cortical and retinal/geniculate light

adaptation resulting in prolonged positive and negative light afterimages, respectively103

.

3.5.4.2. Dysfunction in motion perception

Motion perception requires high-level cortical processing and precise coordination between

multiple regions of the brain, with a large emphasis on MT/MST (medial temporal/medial superior

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temporal areas). Visual trailing is reported during object movement, observer movement, and eye

movement, with or without fixation, suggesting a dysfunction in global motion processing mechanisms.

Visual masking and corollary discharges are inhibitory mechanisms which reduce normal motion blur

from object movement and from eye movement. They are best studied in saccades (saccadic

suppression) but are also present in smooth pursuit and blinking15,28,29,32,52,143,150

.

Visual masking is a phenomenon characterized by the reduction in visibility of an object caused

by the appearance of a second object in space or time. The presentation of a second stimulus can

obscure the perception of a previous stimulus, or the leading edge of a moving object can mask the back

end of the same object which removes visual trails43,99,112

. The masked visual trails are removed from

perceptual awareness but are still processed, helping determine the direction of the motion. Perhaps

persistent, diffuse neuronal hyperexcitability causes failed visual masking and blurred visual trails.

Kilpatrick et al report that visual trailing could result from a group of V1 neurons that stay persistently

active79

. There is currently debate whether visual masking involves active or passive cortical

inhibition84,99,150

.

A corollary discharge is an internal duplicated copy of an efferent signal which notifies other

neurons of impending muscle movement. Corollary discharges help integrate eye movements with

neuro-anatomically segregated processes such as visual attention39

. A well-characterized saccadic

corollary discharge originates in the superior colliculus, synapses in the pulvinar, and proceeds to

MT/MST to inhibit motion processing during the saccade150

. The visual system then integrates pre-

suppression and post-suppression images to create seamless motion105

. A failure to assimilate this

information could result in discontinuous visual trails and akinetopsia. Perhaps diffuse hyperexcitability

causes prominent pre-suppression images, or incomplete/inappropriate corollary discharges do not

properly activate the cortical areas associated with image integration. Shepherd reports that enhanced

motion after-effects in migraineurs are associated with extended suppression130

.

3.6. Etiology: Migraine

There are six cases of palinopsia from migraines, all of which described illusory

palinopsia47,96,117,134,B

. These illusory palinoptic symptoms are often continuous and co-exist with the

other simple visual hallucinations and visual illusions of a migraine aura such as dysmetropsia,

oscillopsia, photopsias, entoptic phenomena, and visual snow. When aura symptoms persist in

migraineurs, the condition is defined by The International Classification of Headache Disorders (ICHD) as

persistent visual aura without infarction142

. Persistent visual aura is further subdivided into typical aura

symptoms (homonymous, gradually developing) such as scotomas and teichopsia and atypical aura

symptoms (diffuse, continuous) such as illusory palinopsia, visual snow, visual trailing, and oscillopsia148

.

Belcastro et al performed a case control study of 200 migraineurs and found that momentary

palinopsia (variant formed image perseveration) occurred in 14.2% of migraineurs with aura and 6.6% of

migraineurs without aura16

. These paroxysmal perseverated images could appear at a different location

in the visual field than the original stimulus, would usually only last a couple of seconds, and occurred a

few times per month. The patients in this study did not complain of other visual symptoms. To note, a

patient on topiramate can have migraine-induced palinopsia, or a patient with migraines can have

topiramate-induced palinopsia.

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3.6.1. Pathophysiology: Cortical spreading depression

Cortical spreading depression (CSD), the presumed cause of a migraine aura, is a wave of intense

depolarizing electrical activity that slowly spreads across cortical grey matter, followed by 1/2 to 2

minutes of suppressed neuronal activity and electrical silence, with eventual repolarization. During the

electrical silence, there is reduced cerebral blood flow, ion homeostasis, decreased extracellular pH, and

intracellular swelling136

. The intense electrical activity could be clinically related to the positive

symptoms (scintillations, tinnitus, tingling) and the subsequent silence to the negative symptoms

(scotomas, hearing loss, paresthesias) of a migraine aura. Following the electrical silence and negative

symptoms, the neuronal repolarization and hyperexcitability would clinically manifest as photophobia,

phonophobia, and cutaneous allodynia. Migraineurs have significant interictal fluctuations in cortical

excitability36

, and most evidence points to a hyperexcitable state being associated with the generation

of the wave of CSD, causing the aura22,23,126,136,138

and perhaps the headache13,110,126

.

The pathophysiology of persistent visual aura is not well-established. Chen et al report ictal

visual cortex excitability potentiation in persistent visual aura compared to ictal habituation in other

migraine types34. Perhaps ictal potentiation and failed cortical adaptation primes the cortex for CSD

wave reverberation, causing the spontaneous and focal symptoms (teichopsia and scotoma) in

persistent aura19,47,148

. Chen et al also report greater interictal visual cortex hyperexcitability in

persistent visual aura than in episodic migraine34

, which could be an effect of the ictal potentiation.

Diffuse, persistent alterations in neuronal excitability would impair light or motion processing, causing

continuous symptoms (illusory palinopsia, visual snow, dysmetropsia, oscillopsia, photophobia). These

diffuse symptoms supports accumulating evidence that emphasizes the role of the thalamus and

brainstem in migraine pathogenesis6,58,109,118

.

The momentary formed perseverated images in as many as 10% of migraineurs are

symptomatically similar to the longer-lasting formed perseverated images from epileptic discharges,

cortical deafferentation, and focal cortical irritation. These migrainous afterimages could represent

localized, transient cortical hyperactivity during a peak in the cyclical cortical excitability state.

Interestingly, Belcastro et al found that migraineurs with these momentary perseverated images

reported significantly fewer migraine attacks (4.3 vs 14.4 attacks/year) than the patients who did not

complain of palinopsia16

. Perhaps the relatively mild, localized, and non-propagating focal electrical

discharge, which generates the momentary afterimage, functions as a failsafe. This could hinder the

production of intensely depolarizing waves of CSD that are associated with the wave propagation, the

prolonged repolarization time, and the subsequent teichopsia, scotoma, and headache.

3.7. Etiology: Head trauma

There are four reports of palinopsia arising after a head injury, all of which described illusory

palinopsia1,50,96,117

. Patients with palinopsia from a traumatic head injury often complain of similar visual

illusions and simple hallucinations as the patients with persistent visual aura and HPPD.

3.7.1 Pathophysiology: Diffuse cortical irritation

Traumatic brain injuries can cause focal or diffuse cortical hyperactivity. Focal hyperactivity and

epilepsy typically require a structural lesion from the head injury101

. The majority of concussion

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symptoms stem from diffuse neuronal dysfunction60

which probably causes diffuse neuronal

hyperexcitability7. Heron et al documented illusory palinopsia, along with other visual illusions and

unformed hallucinations after six days of perceptual isolation62

.

3.8. Etiology: Psychiatric conditions

There are four cases in the literature that report palinopsia from psychiatric conditions:

schizophrenia100

, psychotic depression56

, and Capgras and Cotard Syndrome74

, and peduncular

hallucinosis78. The patient with psychotic depression described repetitively seeing a visual hallucination

(not palinopsia), the patient with peduncular hallucinosis described complex visual hallucinations (not

palinopsia), and the patient with Capgras and Cotard syndrome described repeatedly seeing his

Doppelganger while psychotic, consistent with the syndrome of subjective doubles (not palinopsia). The

patient with schizophrenia reported palinopsia while not overtly psychotic, stating that the palinopsia

worsened when stressed, tired, or prior to a psychotic episode.

3.9. Idiopathic palinopsia

There are five cases of idiopathic palinopsia20,104,117

. There are ICHD classifications for typical

visual aura with non-migraine headache, typical visual aura with no headache, and persistent visual aura

without infarction142

. Therefore, palinopsia without the associated migraine headache could conceivably

be analogous to persistent aura with non-migraine headache or persistent aura with no headache.

Cortical spreading depression also occurs during acute cortical insults40

, so palinopsia and other visual

illusions and hallucinations could theoretically arise from insignificant or silent infarctions.

3.10 Visual snow clinical syndrome

Schankin at al recently dubbed “visual snow clinical syndrome” to describe patients with

refractory symptoms, which they characterized as visual snow along with momentary formed image

perseveration (86%), photopsia (63%), floaters (81%), visual trailing (60%), photophobia (74%),

nyctalopia (68%), tinnitus (62%), blue field entopic phenomena (79%), concentration problems (60%),

and lethargy (55%)125

. Schankin et al report that 59% of the patients have a history of migraines, 87%

have a history of headaches, and 36% describe symptoms starting directly after a migraine125

. Various

combinations of the aforementioned symptoms, with or without visual snow, often co-exist with other

diffuse illusory symptoms (oscillopsia, halos, dysmetropsia) in atypical persistent visual aura, in HPPD, as

a prescription drug side effect, after head trauma, or can be idiopathic1,20,29,47,50,53,65,88,94,96,117,120,134.

The atypical persistent visual aura with the diffuse, illusory symptoms is often harder to treat

than the typical persistent visual aura with scotomas and teichopsia148

. If these continuous and

refractory symptoms (which often agitate the patient) represent a clinical entity, then perhaps more

information on symptom pathogenesis and treatment is needed to determine if visual snow should be

classified separately from the associated persistent diffuse symptoms (including illusory palinopsia) with

the same etiologies.

4. Relationship between pathophysiology, etiology, and symptomology

4.1. Correlation between pathophysiology, etiology, and symptomology

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Reflecting the etiology and symptomology, we now split the pathophysiology of palinopsia into

two categories: dysfunction of visual memory and dysfunction of visual perception (Figure 2).

4.1.1. Dysfunction of visual memory

Hallucinatory palinopsia (formed image perseveration, scene perseveration, categorical

incorporation, patterned visual spread) is indicative of a dysfunction in visual memory, focal cortical

hyperactivity due to post-geniculate lesions or seizures. Cortical deafferentation, epileptic discharges, or

focal irritation cause unregulated or uncontrolled depolarizations and persistent or recurrent activation

of post-geniculate neurons that function in visual memory encoding, processing, or retrieval50

(Figure 2),

Environmental conditions or external parameters will not usually alter the afterimage, implying that the

objects, features, or scenes are already encoded in visual memory. The perseverated images can occur

at a different location in the visual field as the original stimulus and are isochromatic, high-resolution,

and long-lasting.

Cortical deafferentation and focal irritation usually cause a few episodes of palinopsia,

suggesting there is quick cortical compensation to reduce the hyperexcitability. If seizures are persistent,

then continual palinoptic episodes occur. Symptoms may present in a patient with EEG-diagnosed

seizures and visual field deficits, after a neurosurgical procedure. This suggests that the focal neuronal

hyperactivity from each mechanism is additive. Of the 56 patients with focal, posterior visual pathway

lesions or seizures, 52 (93%) described hallucinatory palinopsia (Appendix).

In categorical incorporation, contextual data from visual association circuits is externally

superimposed onto other objects, indicating pathology in visual memory and processing. All of the

hallucinatory palinopsia symptoms can occur concomitantly in a patient with one lesion, which supports

current evidence that objects, features, and scenes are all units of visual memory21

, perhaps at different

levels of processing. This alludes to neuroanatomical integration in visual memory creation and storage.

4.1.2. Dysfunction of visual perception

Illusory palinopsia (visual trailing, light streaking, prolonged indistinct afterimages, momentary

formed image perseveration) is indicative of a dysfunction of visual perception, probably caused by

diffuse, persistent alterations in excitability which can occur after head trauma, after hallucinogen use,

and in migraineurs. There could be a dysfunction in adaptation and feedback between the anterior and

posterior visual pathways. The altered brain state likely affects physiological mechanisms of light or

motion perception, as the perseverated images are heavily dependent on parameters such as eye

fixation, stimulus intensity, background contrast, and motion (Figure 2). Symptoms are often continuous

or predictable and occur at the same location in the visual field as the original stimulus. These

perseverated images tend to be blurry or short-lived. Of the 50 cases of palinopsia that are idiopathic or

attributed to migraines, HPPD, prescription drugs, or head trauma, 47 (94%) described illusory

palinopsia (Appendix).

Symptoms are often worse with high stimulus intensity, a high contrast ratio, and a dark-

adapted state. One patient frequently has symptoms that represent dysfunction in light and motion

perception, even though light and motion are processed via different pathways. This suggests diffuse or

global involvement of visual pathway. Some evidence suggests that patients with persistent illusory

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phenomena also have high rates of cognitive deficits125

, which implies an altered brain state beyond the

visual pathway.

4.2. Overlap in dysfunction of visual memory and visual perception

There is mechanistic commonality in palinopsia since all the proposed mechanisms focus on

dysfunction of neuronal excitability and activity. The features of each symptomatic group are typical

descriptions, not strict guidelines, and there are cases that describe patients with characteristics from

both groups. We used the clarity and duration of the perseverated images as the predominant

determining factors. For example, one case reported hallucinatory palinopsia lasted 30-90 seconds but

was more pronounced after fixation and with high contrast37

. Another case of hallucinatory palinopsia

(from trazodone) described blurred but formed afterimages that required movement, were worse in the

morning, swirled, and lasted 15minutes66

. One patient had unpredictable, paroxysmal episodes of visual

trailing1. A patient with PCA and severe occipital pole atrophy reported that objects would appear in the

complementary color of a previously-viewed bright stimulus33

, which is probably a mix of patterned

visual spread and prolonged physiological afterimages.

The long-lasting black or translucent afterimages in multiple sclerosis and the momentary

afterimages common in migraineurs do not quite fit into either group. These perseverated images are

affected by external parameters and often co-exist with illusory symptoms16,71,B

. The brief, positive, and

formed afterimages in migraineurs were included in illusory palinopsia to simplify the clinical and

prognostic picture. Yet if caused by transient, focal cortical hyperactivity from CSD, they are

mechanistically more similar to hallucinatory palinopsia. Further study of these afterimages in relation

to alterations in cortical excitability could help expose mechanisms associated with the encoding of

visual memory.

5. Clinical encounter

It is important to recognize that palinopsia is a collection of symptoms, not a diagnosis. The

diversity in the etiologies of palinopsia necessitates a thorough history, physical exam, and work-up.

5.1. Clinical history

The clinical history of the palinopsia provides much prognostic information. One should

determine if the palinopsia is illusory or hallucinatory, inquiring about the length, content, and color of

the persisting images or scenes, the time delay between the original stimulus and the palinoptic image,

the number of episodes, the time of day, the place in the visual field where the original and

perseverated image occurred, and if light or motion exacerbates or exposes the palinopsia.

One should take a careful headache history since migraines, cerebrovascular accidents, visual

seizures, and neoplasms can all cause palinopsia. The examiner should ask about the associated

headache symptoms and ask about symptoms related to possible ictal events such as focal neurological

signs, tongue biting, incontinence, nausea/vomiting, and other positive and negative visual phenomena.

Patients complaining of black or translucent afterimages should specifically be asked about findings

associated with multiple sclerosis such as optic neuritis or spasticity.

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A detailed medical and surgical history is important, with emphasis on ophthalmological,

neurological, and psychiatric illnesses and procedures and their relationship to the onset of the

palinopsia. The examiner should also get a detailed prescription drug history, looking for

antidepressants, topiramate, clomiphene, contraceptives, and risperidone. One should ask about a

history of head trauma and a past hallucinogenic drug use, especially in a patient who complains of

illusory palinopsia with a clinical history that does not suggest any other etiologies.

5.2. Physical exam

Palinopsia necessitates proper ophthalmological and neurological physical exams. Visual acuity,

pupils, tonometry, extraocular movements, external exam, and anterior chamber exam are usually

noncontributory. Bedside or formal visual fields may show deficits in cases with structural lesions.

Funduscopy is typically normal but may reveal papilledema if the underlying etiology causes significant

mass effect. The neurological exam including cranial nerves, deep tendon reflexes, sensation, motor,

and cerebellar testing is often normal since the pathology (if present) is often in the visual pathway.

5.3 Work-up and Diagnosis

Visual fields and neuroimaging should usually be obtained in patients with palinopsia. Routine

labs such as a complete metabolic panel and complete blood count may be done to check for metabolic

disturbances or hint at the presence of a neoplasm. Other diagnostic tests such as structural or

functional neuroimaging, EEG, electroretinogram, visual evoked potential, lumbar puncture, or drug

screen should be performed on an as-needed basis, depending on the clinical history, the results of the

preliminary work-up, the working diagnosis, and the symptom persistence.

5.3.1. Hallucinatory palinopsia

It is generally easy to diagnose the primary cause of hallucinatory palinopsia, the symptoms

indicative of a dysfunction of visual memory. Neuroimaging will usually reveal cortical lesions. In

patients with unremarkable neuroimaging, blood tests and clinical history will often expose the

pathology. An EEG can be performed if epileptic discharges are suspected by the clinical history, or there

is a long latency between the original and palinoptic image, multiple recurrences of the same

perseverated image or scene, or continual episodes of hallucinatory palinopsia.

One should be cognizant of hallucinatory palinopsia symptoms, which can be the presenting

symptom of a potentially life-threatening illness116,154. If the primary work-up is negative, there should

be a short follow-up. One patient who experienced an episode of formed image perseveration with

unremarkable neuroimaging was diagnosed five months later with a glioblastoma multiforme82

. Another

patient was later diagnosed with CJD119

. Occasionally, hallucinatory palinopsia is drug-related or caused

by TIAs, and the patient would continue to have negative diagnostic testing.

5.3.2. Illusory palinopsia Illusory palinopsia, symptoms indicative of a dysfunction in visual perception, is usually due to

pharmaceutical drugs, HPPD, migraines, or head trauma. The physical exam and work-up are almost

always non-contributory, and diagnosis is largely based on information from the clinical history.

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Palinopsia is attributed to a prescription drug if symptoms begin after initiation or dose increase.

Continuous illusory palinopsia in a migraineur is usually persistent migrainous aura. HPPD is a diagnosis

of exclusion in patients with a history of hallucinogen use. Migraines and HPPD are probably the most

common causes of palinopsia, despite the paucity of case reports in the literature.

If the history and work-up do not reveal an etiology, then the idiopathic palinopsia may be

analogous to the cerebral state in persistent visual aura with non-migraine headache or persistent visual

aura with no headache. Because of the subjective nature of the symptoms and the absence of organic

findings, doctors are sometimes dismissive of patients with illusory palinopsia, which may cause the

patients considerable distress. There is substantial evidence in the literature verifying the symptom

legitimacy, so validating the patient’s symptoms can alleviate anxiety.

5.3.3. Exceptions to palinopsia groupings

Five patients (with schizophrenia, infarction, neoplasm, HPPD, idiopathic) had symptoms from

both groups (Appendix), and a few patients had a diagnosis in the opposite group as would be

predicated by symptomology. Patients with illusory palinopsia from cortical lesions or seizures usually

have other alarming symptoms such as neurological deficits or complex visual hallucinations37,75

.

Unidirectional visual trails, symptoms confined to part of a visual field, or homonymous field loss

suggests focal cortical pathology. One patient had a left-sided infarction in MT/MST causing only

rightward akinetopic visual trails57

. Two patients with PCA had severe right-sided parietal atrophy and

only leftward akinetopic visual trails144

. Another patient with occipital and LGN infarctions had light

streaking confined to the quadrant with the field deficit145

.

Risk factors for possible serious pathology include old age, vasculopathy, a history of cancer, and

a history of radiation. It is reasonable to order neuroimaging in illusory palinopsia, as migraine aura

symptoms can mimic seizures or posterior cortical lesions63,113,122,128

. In a young patient with illusory

palinopsia and no other worrisome symptoms or signs, neuroimaging is low-yield but may provide the

patient peace of mind. Belcastro et al reported that as many as 10% of migraineurs have isolated

episodes of momentary formed image perseveration16

. If this data is corroborated, then these patients

might not need additional neuroimaging.

There are not any reported cases of palinopsia from cancer-associated retinopathy or

metabolic/toxic retinopathy, but there are reports of related illusory symptoms in these occult

conditions. Further retinal work-up might be indicated in a patient presenting with palinopsia and a

suggestive clinical history.

5.4. Treatment

Palinopsia from CVAs typically resolves spontaneously and treatment should be directed at the

vasculopathic risk factors. Neoplasms, AVMs, or abscesses require treatment of the underlying

condition, which usually also resolves the palinopsia. Palinopsia due to seizures generally resolves after

correcting the primary disturbance and/or treating the seizures. The literature reports success with

carbamazepine or phenytoin, but newer, less toxic drugs with similar seizure-aborting ability could likely

be used. In persistent hallucinatory palinopsia, a trial of an anti-epileptic drug may be attempted since

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there could be undiagnosed seizures. Drugs that reduce cortical excitability could also potentially treat

palinopsia caused by deafferentation or irritation.

Palinopsia from prescription drugs is treated by discontinuing the offending agent, although this

is only necessary in drugs reported to cause permanent symptoms (clomiphene and oral

contraceptives). If symptoms are not bothersome and there is a positive therapeutic response, the

patient may elect to continue the drug. There is no standard treatment for HPPD, and no randomized

controlled trials have been performed. The condition is generally benign, so treatment is based on the

patient’s distress and willingness to try multiple trials of different drugs. Case series of 7-9 patients show

an 80%+ cure rate from benzodiazepines, clonidine, and haloperidol for HPPD59

. Given the side-effect

profile of haloperidol and the abuse potential of benzodiazepines, these drugs are not optimal for

treating a benign condition. Additionally, Lerner et al report that the trailing phenomenon is

“remarkably refractory” to clonazepam93

. There are reports of selective serotonin reuptake inhibitors

and risperidone exacerbating HPPD5,59

.

There is even less evidence for treating persistent migrainous aura without infarction. There are

single cases which report successful treatment with lamotrigine, nimodipine, topiramate, verapamil,

divalproex sodium, gabapentin, furosemide, and acetazolamide, as these drugs have mechanisms that

decrease neuronal excitability34,134

. Others report treatment failure from the same drugs. Some report

that treating the migraine improves the persistent aura symptoms, while others report no effect47. The

focal, typical persistent visual aura symptoms are usually easier to treat than the diffuse atypical

persistent visual aura symptoms148

.

It is not clear if the etiology of the illusory palinopsia affects treatment efficacy, but given the

symptom similarity, it is reasonable to try the same pharmaceuticals to treat the illusory symptoms from

persistent migrainous aura, HPPD, head trauma, and idiopathic palinopsia. Based on the available

evidence and side-effect profile, clonidine might be an attractive treatment option. Richter et al show

that clonidine suppresses CSD in rats121, and indirect evidence shows that clonidine reduces cortical

hyperexcitability31,95

. Other drugs with relatively benign side effect profiles may also be attempted, if

desired by the patient. Since many patients report improvement from sunglasses, one could suggest

trying the FL-41 tinted lenses which have shown some efficacy in treating visually sensitive

migraineurs151

.

6. Conclusion

Palinopsia is not a diagnosis, but a broad term that describes a heterogeneous group of

symptoms. We divided the symptoms into two clinically relevant categories. Hallucinatory palinopsia

consists of formed image perseveration, scene perseveration, categorical incorporation, and patterned

visual spread. These symptoms typically arise from post-geniculate cortical lesions and various seizure

etiologies and resolve after treating the underlying pathology. The perseverated images are long-lasting,

high clarity, isochromatic, and not typically affected by light or motion. Hallucinatory palinopsia is the

result of posterior visual pathway deafferentation, epileptic discharges, or focal cortical irritation, which

likely cause focal cortical hyperexcitability or hyperactivity and inappropriate and persistent activation

of a visual memory circuit (Figure 2). If no etiology is found, these alarming symptoms warrant further

testing or prompt follow-up. This was previously considered a dorsal stream disorder in the non-

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dominant parieto-occipital l lobe, but the predominance of lesions in certain cortical areas is more likely

due to the uneven distribution or functional variation of visual cortex-hippocampal neurons.

Illusory palinopsia consists of momentary formed image perseveration, prolonged indistinct

afterimages, light streaking, and visual trailing (Figure 2). The perseverated images short-lived or

unformed, occur in the same location in the visual field as the original stimulus, and are affected by

fixation, light, and motion. Migraines (persistent migrainous aura), HPPD, prescription drugs, and head

trauma are the known etiologies, but the palinopsia can also be idiopathic. Combinations of the illusory

palinoptic symptoms often co-exist with simple visual hallucinations and with other diffuse, illusory

symptoms such as visual snow, dysmetropsia, and oscillopsia. These symptoms are presumably related

to a diffuse modification in neuronal sensitivity or excitability. More evidence is needed on the efficacy

of pharmaceuticals for these various symptoms and diagnoses, but clonidine, gabapentin,

acetazolamide, magnesium, or calcium channel blockers could be possible treatment options.

7. Method of literature search

We conducted a PubMed and Web of Science search of the English language literature using the

search terms palinopsia, paliopsia, visual perseveration, cerebral polyopia, illusory visual spread, visual

trails, visual snow, visual trailing, hallucinogen persisting perception disorder, positive spontaneous

visual phenomena, akinetopsia, and dyskinetopsia from 1968 to the present. Reference lists from

retrieved articles were examined for additional citations. The accepted definition of palinopsia was

described in 1968, and neuroimaging was not available which caused difficulty in diagnosis before that

time. Cases that did not adequately describe symptoms were excluded from numerical analysis

(Appendix). Non-case articles describing palinoptic mechanisms were reviewed as needed.

8. Disclosures

The authors report no proprietary or commercial interests in any product or concept discussed

in this article.

9. References

1. Abert B, Ilsen PF. Palinopsia. Optometry. 2010;81(8):394-404

2. Abraham HD. Visual phenomenology of the LSD flashback. Arch Gen Psychiatry. 1983;40(8):884-9

3. Abraham HD, Aldridge AM, Gogia P. The psychopharmacology of hallucinogens.

Neuropsychopharmacology. 1996;14(4):285-98

4. Abraham HD, Duffy FH. Stable quantitative EEG difference in post-LSD visual disorder by split-half

analysis: evidence for disinhibition. Psychiatry Res. 1996;67(3):173-87

5. Abraham HD, Mamen A. LSD-like panic from risperidone in post-LSD visual disorder. J Clin

Psychopharmacol. 1996;16(3):238-41

6. Akerman S, Holland PR, Goadsby P J. Diencephalic and brainstem mechanisms in migraine. Nat Rev

Neurosci. 2011;12(10):570-84

7. Alwis DS, Johnstone V, Yan E, Rajan R. Diffuse traumatic brain injury and the sensory brain. Clin Exp

Pharmacol Physiol. 2013;40(7):473-83

8. Anbarasan D., Howard J. Acute exacerbation of multiple sclerosis presenting with facial

metamorphopsia and palinopsia. Mult Scler. 2013;19(3):369-71

9. Anderson WH, O'Malley JE. Trifluoperazine for the "trailing" phenomenon. Jama. 1972;220(9):1244-5

MANUSCRIP

T

ACCEPTED

ACCEPTED MANUSCRIPT20

10. Ardila A, Botero M, Gomez J. Palinopsia and visual allesthesia. Int J Neurosci. 1987;32(3-4):775-82

11. Arnold RW, Janis B, Wellman S, Crouch E, Rosen C. Palinopsia with bacterial brain abscess and

Noonan syndrome. Alaska Med. 1999;41(1):3-7

12. Aurora SK, Barrodale PM, Vermaas AR, Rudra CB. Topiramate modulates excitability of the occipital

cortex when measured by transcranial magnetic stimulation. Cephalalgia. 2010;30(6):648-54

13. Aurora SK, Wilkinson F. The brain is hyperexcitable in migraine. Cephalalgia. 2007;27(12):1442-53

14. Baggott MJ, Coyle JR, Erowid E, Erowid F, Robertson LC. Abnormal visual experiences in individuals

with histories of hallucinogen use: a Web-based questionnaire. Drug Alcohol Depend. 2011;114(1):61-6

15. Barnes GR. Cognitive processes involved in smooth pursuit eye movements. Brain Cogn.

2008;68(3):309-26

16. Belcastro V, Cupini LM, Corbelli I et al. Palinopsia in patients with migraine: a case-control study.

Cephalalgia. 2011;31(9): 999-1004

17. Bender MB, Feldman M, Sobin A J. Palinopsia. Brain. 1968;91(2): 321-38

18. Bender MB, Sobin AJ. Polyopia and palinopsia in homonymous fields of vision. Trans Am Neurol

Assoc. 1963;88:56-9

19. Bereczki D, Kollar J, Kozak N et al. Cortical spreading edema in persistent visual migraine aura.

Headache. 2008;48(8):1226-9

20. Blythe IM, Bromley JM, Ruddock KH, Kennard C, Traub M. A study of systematic visual perseveration

involving central mechanisms. Brain. 1986;109(4):661-75

21. Brady TF, Konkle T, Alvarez GA. A review of visual memory capacity: Beyond individual items and

toward structured representations. J Vis. 2011;11(5):1-34

22. Brigo F, Storti M, Nardone R et al. Transcranial magnetic stimulation of visual cortex in migraine

patients: a systematic review with meta-analysis. J Headache Pain. 2012;13(5):339-49

23. Brigo F, Storti M, Tezzon F, Manganotti P, Nardone R. Primary visual cortex excitability in migraine: a

systematic review with meta-analysis. Neurol Sci. 2013;34(6): 819-30

24. Brindley GS. Two new properties of foveal after-images and a photochemical hypothesis to explain

them. J Physiol. 1962;164:168-79

25. Brust JC, Behrens MM. "Release hallucinations" as the major symptom of posterior cerebral artery

occlusion: a report of 2 cases. Ann Neurol. 1977;2(5):432-6

26. Burgess N, Maguire EA, O'Keefe J. The human hippocampus and spatial and episodic memory.

Neuron. 2002;35(4):625-41

27. Burke W. The neural basis of Charles Bonnet hallucinations: a hypothesis. J Neurol Neurosurg

Psychiatry. 2002;73(5):535-41

28. Burr D. Motion smear. Nature. 1980;284(5752):164-5

29. Burr D. Vision: in the blink of an eye. Curr Biol. 2005;15(14), R554-6

30. Bynke H. Visual perseveration following temporal lobe surgery Case report. Neuro-Ophthalmology.

1985;4(1):47-53

31. Calligaris L, Vidoni A, Bruno I, Vidoni M, Barbi E. Efficacy of clonidine in hyperammonemia induced

hyperexcitability syndrome. Paediatr Anaesth. 2013;23(2):202-4

32. Cambron M, Anseeuw S, Paemeleire K, Crevits L. Saccade behavior in migraine patients. Cephalagia.

2011;31(9):1005-14

33. Chan D, Crutch SJ, Warrington EK. A disorder of colour perception associated with abnormal colour

after-images: a defect of the primary visual cortex. J Neurol Neurosurg Psychiatry. 2001;71(4):515-7

34. Chen WT, Lin YY, Fuh JL, Hamalainen MS, Ko YC, Wang SJ. Sustained visual cortex hyperexcitability in

migraine with persistent visual aura. Brain. 2011;134(8):2387-95

35. Cleland PG, Saunders M, Rosser R. An unusual case of visual perseveration. J Neurol Neurosurg

Psychiatry. 1981;44(3):262-3

MANUSCRIP

T

ACCEPTED

ACCEPTED MANUSCRIPT21

36. Cosentino G, Fierro B, Vigneri S et al (in press). Cyclical changes of cortical excitability and

metaplasticity in migraine: evidence by a rTMS study. Pain.

37. Cummings JL, Syndulko K, Goldberg Z, Treiman DM. Palinopsia reconsidered. Neurology. 1982;

2(4):444-7

38. Curio M, Popovic J, Pignatti R, Sacco L. Case report - Palinopsia in a patient with a left pericalcarine

cavernous haemangioma. Swiss Archives of Neurology and Psychiatry. 2012;163(7): 255-6

39. Deubel H, Schneider WX. Saccade target selection and object recognition: evidence for a common

attentional mechanism. Vision Res. 1996;36(12): 1827-37

40. Dreier JP. The role of spreading depression, spreading depolarization and spreading ischemia in

neurological disease. Nat Med. 2011;17(4):439-47

41. Dubois J, Vanrullen R. Visual trails: do the doors of perception open periodically? PLoS Biol.

2011;9(5):e1001056

42. Engelsen BA, Tzoulis C, Karlsen B et al. POLG1 mutations cause a syndromic epilepsy with occipital

lobe predilection. Brain. 2008;131(3):818-28

43. Enns JT, Di Lollo V. What's new in visual masking? Trends Cogn Sci. 2000;4(9):345-52

44. Enroth-Cugell C, Robson JG. The contrast sensitivity of retinal ganglion cells of the cat. J Physiol.

1966;187(3):517-52

45. Eretto PA, Schoen FS, Krohel GB, Pechette D. Palinoptic visual allesthesia. Am J Ophthalmol.

1982;93(6):801-3

46. Evans RW. Reversible palinopsia and the Alice in Wonderland syndrome associated with topiramate

use in migraineurs. Headache. 2006;46(5):815-8.

47. Evans RW, Aurora SK. Migraine with persistent visual aura. Headache. 2012;52(3):494-501

48. Faber RA, Benzick JM. Nafazodone-induced palinopsia. J Clin Psychopharmacol. 2000;20(2):275-6

49. Fontenelle LF. Topiramate-induced palinopsia. Int J Neuropsychiatry Clin Neurosci. 2008;20(2):249-

50

50. Fournier AV, Zackon DH. Palinopsia: a case report and review of the literature. Can J Ophthalmol.

200;35(3):154-7

51. Friedman DI, Hu EH, Sadun AA. Neuro-ophthalmic complications of interleukin 2 therapy. Arch

Ophthalmol. 1991;109(12):1679-80

52. Furman M, Gur M. And yet it moves: perceptual illusions and neural mechanisms of pursuit

compensation during smooth pursuit eye movements. Neurosci Biobehav Rev. 2012; 36(1):143-51

53. Gaillard MC, Borruat FX. Persisting visual hallucinations and illusions in previously drug-addicted

patients. Klin Monbl Augenheilkd. 2003;220(3):176-8

54.Garcia-Perez MA, Peli E. Visual Contrast Processing is Largely Unaltered during Saccades. Front

Psychol. 2011;2:247

55. Gardner JL, Sun P, Waggoner RA et al.Contrast adaptation and representation in human early visual

cortex. Neuron. 2005;47(4):607-20

56. Gates TJ, Stagno SJ, Gulledge AD. Palinopsia posing as a psychotic depression. Br J Psychiatry.

1988;153:391-3

57. Gottlieb D. The unidirectionality of cerebral polyopia. J Clin Neuroophthalmol. 1992;12(4):257-62

58. Granziera C, Daducci A, Romascano D et al (in press). Structural abnormalities in the thalamus of

migraineurs with aura: A multiparametric study at 3 T. Hum Brain Mapp.

59. Halpern JH, Pope HG. Hallucinogen persisting perception disorder: what do we know after 50 years?

Drug Alcohol Depend. 2003;69(2):109-19

60. Hardman JM, Manoukian A. Pathology of head trauma. Neuroimaging Clin N Am. 2002;12(2):175-87

61. Hayashi R, Shimizu S, Watanabe R, Katsumata Y, Mimura M. Palinopsia and perilesional

hyperperfusion following subcortical hemorrhage. Acta Neurol Scand. 2002;105(3):228-31

MANUSCRIP

T

ACCEPTED

ACCEPTED MANUSCRIPT22

62. Heron W, Doane BK, Scott TH. Visual disturbances after prolonged perceptual isolation. Can J

Psychol. 1956;10(1):13-8

63. Hoffman JA. LSD flashbacks. Arch Gen Psychiatry. 1984;41(6):631-2

64. Hori H, Terao T, Nakamura J. Visual perseveration: a new side effect of maprotiline. Acta Psychiatr

Scand. 2002;101(6): 476-7

65. Horton JC, Trobe JD. Akinetopsia from nefazodone toxicity. Am J Ophthalmol. 1999;128(4):530-1

66. Hughes MS, Lessell S. Trazodone-induced palinopsia. Arch Ophthalmol. 1990;108(3):399-400

67. Hundal KS, Chen S, Moore W, Tranos P, Joshi N. Dyskinetopsia during light adaptation associated

with nefazodone treatment. Eye (Lond). 2003;17(9):1040-2.

68. Ihde-Scholl T, Jefferson JW. Mitrazapine-associated palinopsia. J Clin Psychiatry. 2001 62(5):373

69. Jacobs L. Visual allesthesia. Neurology. 1980;30(10):1059-63

70. Jacobs L, Feldman M, Bender MB. The persistence of visual or auditory percepts as symptoms of

irritative lesions of the cerebrum of man. Z Neurol. 1972;203(3): 211-8

71. Jacome DE. Palinopsia and bitemporal visual extinction on fixation. Ann Ophthalmol. 1985;17(4),

251-2

72. Johnson SF, Loge RV. Palinopsia due to nonketotic hyperglycemia. West J Med. 1988;148(3):331-2

73. Jones MR, Waggoner R, Hoyt WF. Cerebral polyopia with extrastriate quadrantanopia: report of a

case with magnetic resonance documentation of V2/V3 cortical infarction. J Neuroophthalmol.

1999;19(1):1-6

74. Joseph AB. Cotard's syndrome in a patient with coexistent Capgras' syndrome, syndrome of

subjective doubles, and palinopsia. J Clin Psychiatr. 1986;47(12):605-6

75. Kataoka H, Ueno S. Cerebral polyopia and palinopsia in a patient with occipital lobe epilepsy.

Epilepsy Behav. 2009 14(4):684-6

76. Kawasaki A, Purvin V. Persistent palinopsia following ingestion of lysergic acid diethylamide (LSD).

Arch Ophthalmol. 1996;114(1):47-50

77. Khan AN, Sharma R, Khalid S et al. Palinopsia from a posteriorly placed glioma--an insight into its

possible causes. BMJ Case Rep. 2011;2011:bcr0820103273

78. Killer HE, Buettner UW. Mulitple Visual hallucinations and pseudohallucinations in on individual

patient: when the world is turning upside down and the television keeps falling to the ground while the

dwarfs are parading on the ceiling. Ophthalmologica. 2005;219(2):115-8

79. Kilpatrick ZP, Bard Ermentrout G. Hallucinogen persisting perception disorder in neuronal networks

with adaptation. J Comput Neurosci. 2012;32(1):25-53

80. Kim H, Chu K, Jung KH et al. Acquired encephalopathy associated with carnitine deficiency after

cefditoren pivoxil administration. Neurol Sci. 2012;33(6):1393-6

81. Kolmel HW. Visual illusions and hallucinations. Baillieres Clin Neurol. 1993;2(2):243-64

82. Kondziella D, Maetzel H. The sting in the tail: syncope and palinopsia. J Neurol. 2006;253(5):657-8

83. Kraus RP. Visual "trails" with nefazodone treatment. Am J Psychiatry. 1996;153(10):1365-6

84. Kupersmith MJ, Berenstein A, Nelson PK, ApSimon HT, Setton A. Visual symptoms with dural

arteriovenous malformations draining into occipital veins. Neurology. 1999;52(1):156-62

85. Lance JW. Simple formed hallucinations confined to the area of a specific visual field defect. Brain.

1976;99(4):719-34

86. Landis T, Cummings JL., Benson DF, Palmer, EP. Loss of topographic familiarity. An environmental

agnosia. Arch Neurol. 1986;43(2):132-6

87. Lang C. Palinoptic phenomena as an error mechanism in resolving alexia without agraphia. A case

report. Eur Neurol. 1985;24(4): 248-53

88. Lauterbach EC, Abdelhamid A, Annandale JB. Posthallucinogen-like visual illusions (palinopsia) with

risperidone in a patient without previous hallucinogen exposure: possible relation to serotonin 5HT2a

receptor blockade. Pharmacopsychiatry. 2002;33(1):38-41

MANUSCRIP

T

ACCEPTED

ACCEPTED MANUSCRIPT23

89. Lazaro RP. Palinopsia: rare but ominous symptom of cerebral dysfunction. Neurosurgery.

1983;13(3):310-3

90. le Grand SM, Supornsilpchai W, Saengjaroentham C, Srikiatkhachorn A. Serotonin depletion leads to

cortical hyperexcitability and trigeminal nociceptive facilitation via the nitric oxide pathway. Headache.

2011;51(7) 1152-60

91. Lefebre C, Kolmel HW. Palinopsia as an epileptic phenomenon. Eur Neurol. 1989;29(6):323-7

92. Leo H, Melanie S, Martin R, Anil B, Martin G. Hallucinogen Persisting Perception Disorder (HPPD) and

flashback- are they identical?. J Alcoholism Drug Depend. 2013;1:4

93. Lerner AG, Gelkopf M, Skladman I et al. Clonazepam treatment of lysergic acid diethylamide-induced

hallucinogen persisting perception disorder with anxiety features. Int Clin Psychopharmacol.

2003;18(2):101-5

94. Levi L, Miller NR. Visual illusions associated with previous drug abuse. J Clin Neuroophthalmol.

1990;10(2):103-10

95. Liu B, Eisenach JC. Hyperexcitability of axotomized and neighboring unaxotomized sensory neurons

is reduced days after perineural clonidine at the site of injury. J Neurophysiol. 2005;94(5):3159-67

96. Liu GT, Schatz NJ, Galetta SL et al. Persistent positive visual phenomena in migraine. Neurology.

1995;45(4):664-8

97. Lopez JR, Adornato BT, Hoyt WF. 'Entomopia': a remarkable case of cerebral polyopia. Neurology.

1993;43(10):2145-6

98. Lunardi P, Tacconi L, Missori P, Salvati M. Palinopsia: unusual presenting symptom of a cerebral

abscess in a man with Kartagener's syndrome. Clin Neurol Neurosurg. 1991;93(4):337-9

99. Marinovic W, Arnold DH. An illusory distortion of moving form driven by motion deblurring. Vision

Res. 2013;88:47-54

100. Marneros A, Korner J. Chronic palinopsia in schizophrenia. Psychopathology. 1993;26(5-6): 236-9

101. McCrory PR, Berkovic SF. Concussive convulsions. Incidence in sport and treatment

recommendations. Sports Med. 1998;25(2): 131-6

102. McGuire PK, Cope H, Fahy TA. Diversity of psychopathology associated with use of 3,4-

methylenedioxymethamphetamine ('Ecstasy'). Br J Psychiatry. 1994;165(3):391-5

103. McLelland D, Baker P, Ahmed B, Bair W. Neuronal responses during and after the presentation of

static visual stimuli in macaque primary visual cortex. J Neurosci. 2010;30(38):12619-31

104. Meadows JC, Munro SS. Palinopsia. J Neurol Neurosurg Psychiatry. 1977;40(1): 5-8

105. Melcher D, Colby CL. Trans-saccadic perception. Trends Cogn Sci. 2008;12(12):466-73

106. Michel EM, Troost BT. Palinopsia: cerebral localization with computed tomography. Neurology.

1980;30(8):887-9

107. Mitsueda-Ono T, Ikeda A, Noguchi E et al. Epileptic polyopia with right temporal lobe epilepsy as

studied by FDG-PET and MRI: a case report. J Neurol Sci. 2006;247(1): 109-11

108. Mosberian P, Leung M, Hollander Y, Remick RA. Nefazodone-induced visual disturbances. Can J

Psychiatry. 1999;44(9):925-6

109. Moulton EA, Burstein R, Tully S et al. Interictal dysfunction of a brainstem descending modulatory

center in migraine patients. PLoS One. 2008;3(11):e3799

110. Mulleners WM, Chronicle EP, Palmer JE, Koehler PJ, Vredeveld JW. Visual cortex excitability in

migraine with and without aura. Headache. 2001;41(6):565-72

111. Muller T, Buttner T, Kuhn W, Heinz A, Przuntek H. Palinopsia as sensory epileptic phenomenon.

Acta Neurol Scand. 1995;91(6):433-6

112. Ogmen H. A theory of moving form perception: Synergy between masking, perceptual grouping,

and motion computation in retinotopic and non-retinotopic representations. Adv Cogn Psychol.

2007;3(1-2):67-84

MANUSCRIP

T

ACCEPTED

ACCEPTED MANUSCRIPT24

113. Ogunyemi A, Adams D. Migraine-like symptoms triggered by occipital lobe seizures: response to

sumatriptan. Can J Neurol Sci. 1998;25(2):151-3

114. Olsen SR, Bortone DS, Adesnik H, Scanziani M. Gain control by layer six in cortical circuits of vision.

Nature. 2012;483(7387):47-52

115. Ossola M, Romani A, Tavazzi E, Pichiecchio A, Galimberti CA. Epileptic mechanisms in Charles

Bonnet syndrome. Epilepsy Behav. 2010;18(1-2):119-22

116. Patterson MC, Bunce IH, Eadie MJ. Cerebral abscess in leukaemia: an unusual presentation of a rare

complication. Clin Exp Neurol. 1985;21:257-62

117. Pomeranz HD, Lessell S. Palinopsia and polyopia in the absence of drugs or cerebral disease.

Neurology. 2000;54(4):855-9

118. Prescot A, Becerra L, Pendse G et al. Excitatory neurotransmitters in brain regions in interictal

migraine patients. Mol Pain. 2009;5:34

119. Purvin V, Bonnin J, Goodman J. Palinopsia as a presenting manifestation of Creutzfeldt-Jakob

disease. J Clin Neuroophthalmol. 1989;9(4):242-8

120. Purvin VA. Visual disturbance secondary to clomiphene citrate. Arch Ophthalmol. 1995;113(4):482-

4

121. Richter F, Mikulik O, Ebersberger A, Schaible HG. Noradrenergic agonists and antagonists influence

migration of cortical spreading depression in rat-a possible mechanism of migraine prophylaxis and

prevention of postischemic neuronal damage. J Cereb Blood Flow Metab. 2005;25(9):1225-35

122. Ritsema ME, Murphy MA. Palinopsia from posterior visual pathway lesions without visual field

defects. J Neuroophthalmol. 2007;27(2):115-7

123. Rossi S, Furlan R, De Chiara V et al. Interleukin-1beta causes synaptic hyperexcitability in multiple

sclerosis. Ann Neurol. 2012;71(1):76-83

124. Rubin EH, de Alwis DP, Pouliquen I et al. A phase I trial of a potent P-glycoprotein inhibitor,

Zosuquidar.3HCl trihydrochloride (LY335979), administered orally in combination with doxorubicin in

patients with advanced malignancies. Clin Cancer Res. 2002; 8(12):3710-7

125. Schankin CJ, Maniyar FH, Digre KB, Goadsby PJ (in press). 'Visual snow' - a disorder distinct from

persistent migraine aura. Brain.

126. Schoenen J. Neurophysiological features of the migrainous brain. Neurol Sci. 2006;27(Suppl 2): 77-

81

127. Schwartz K. Nefazodone and visual side effects. Am J Psychiatry. 1997;154(7):1038

128. Shams PN, Plant GT. Migraine-like visual aura due to focal cerebral lesions: case series and review.

Surv Ophthalmol. 2011;56(2):135-61

129. Shen RY, Andrade R. 5-Hydroxytryptamine2 receptor facilitates GABAergic neurotransmission in rat

hippocampus. J Pharmacol Exp Ther. 1998;285(2):805-12

130. Shepherd AJ. Increased visual after-effects following pattern adaptation in migraine: a lack of

intracortical excitation? Brain. 2001;124(11):2310-8

131. Shimojo S, Kamitani Y, Nishida S. Afterimage of perceptually filled-in surface. Science.

2001;293(5535):1677-80

132. Sierra-Hidalgo F, de Pablo-Fernandez E. Palinopsia induced by topiramate and zonisamide in a

patient with migraine. Clin Neuropharmacol. 2013;36(2):63-4

133. Silva JA, Tekell JL, Penny G, Bowden CL. Resolution of palinopsia with carbamazepine. J Clin

Psychiatry. 1997;58(1):30

134. Simpson JC, Goadsby PJ, Prabhakar P. Positive persistent visual symptoms (visual snow) presenting

as a migraine variant in a 12-year-old girl. Pediatr Neurol. 2013;49(5):361-3

135. Smith PE, Shah P, Sharpe J, Todd A, Goringe AP. Palinopsia. Lancet. 2003;361(9363):1098

136. Somjen GG. Mechanisms of spreading depression and hypoxic spreading depression-like

depolarization. Physiol Rev. 2001;81(3):1065-96

MANUSCRIP

T

ACCEPTED

ACCEPTED MANUSCRIPT25

137. Stagno SJ, Gates TJ. Palinopsia: a review of the literature. Behav Neurol. 1991;4(2):67-74

138. Stankewitz A, May A. Cortical excitability and migraine. Cephalalgia. 2007;27(12):1454-6

139. Sun YT, Lin CC. Sequential appearance and disappearance of hemianopia, palinopsia and

metamorphopsia: a case report and literature review. Acta Neurol Taiwan. 2004;13(2):77-83

140. Sunness JS. Persistent afterimages (palinopsia) and photophobia in a patient with a history of LSD

use. Retina. 2004;24(5):805

141. Swash M. Visual perseveration in temporal lobe epilepsy. J Neurol Nuerosurg Psychiatry. 1979;

42(6):569-71

142. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalagia.

2013;33(9)629-808

143. Thiele A, Henning P, Kubischik M, Hoffmann KP. Neural mechanisms of saccadic suppression.

Science. 2002;295(5564):2460-2

144. Tsai PH, Mendez MF. Akinetopsia in the posterior cortical variant of Alzheimer disease. Neurology.

2009;73(9):731-2

145. Van der Stigchel S, Nijboer TC, Bergsma DP, Barton JJ, Paffen CL. Measuring palinopsia:

characteristics of a persevering visual sensation from cerebral pathology. J Neurol Sci. 2012;316(1-

2):184-8

146. Vaphiades, MS, Celesia GG, Brigell MG. Positive spontaneous visual phenomena limited to the

hemianopic field in lesions of central visual pathways. Neurology. 1996;47(2):408-17

147. Virsu V. Retinal mechanisms of visual adaptation and afterimages. Med Biol. 1978;56(2):84-96

148. Wang YF, Fuh JL, Chen WT, Wang SJ. The visual aura rating scale as an outcome predictor for

persistent visual aura without infarction. Cephalalgia. 2008;28(12):1298-1304

149. Werring DJ, Marsden CD. Visual hallucinations and palinopsia due to an occipital lobe tuberculoma.

J Neurol Neurosurg Psychiatry. 1999;66(5):684

150. Wurtz RH. Neuronal mechanisms of visual stability. Vision Res. 2008;48(20):2070-89

151. Wilkins AJ, Patel R, Adjamian P, Evans BJ. Tinted spectacles and visually sensitive migraine.

Cephalagia. 2002;22(9):711-9

152. Young WB, Heros DO, Ehrenberg, B. L., Hedges TR. Metamorphopsia and palinopsia. Association

with periodic lateralized epileptiform discharges in a patient with malignant astrocytoma. Arch Neurol.

1989;46(7):820-2

153. Zakaria A, Lalani I, Belorgey L, Jay Foreman P. Focal occipital seizures with cerebral polyopia.

Epileptic Disord. 2006;8(4):295-7

154. Ziaei M, Elgohary MA, Bremner FD. Palinopsia as the initial manifestation of non-hodgkin's

lymphoma. Int Ophthalmol. 2013;33(5):553-6

Other Cited Material

A. Metz RJ, Pieri V, Diederich NJ. Object-specific and “side inversed” palinopsia limited to the

hemianopic field in occipital infarction. Poster session presented at: 16th

Meeting of the European

Neurological Society; 2006 May 27-31; Luxembourg, LUX

B. Abdulfattah Q, Swanson JW. Migraine headache and palinopsia. Poster session presented at: 47th

Annual Scientific Meeting American Headache Society; 2005 Jun 23-5; Philadelphia, PA

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Figure 1- Examples of palinopsia symptom types. (A) Formed image perseveration: an examiner’s hand

persists in the visual field. (B) Categorical incorporation: a spire is incorporated on to other buildings.

(C) Visual trailing: a ball in motion leaves images in its wake. Photographs courtesy of Kelli X. Gross, MD.

Figure 2- Flowchart contrasting the two types of palinopsia. Hallucinatory palinopsia is caused by a

dysfunction in visual memory and illusory palinopsia is caused by a dysfunction in visual perception.

HPPD = hallucinogen persisting perception disorder.

Appendix- Details the 129 cases of palinopsia we found in the literature. * = Cases of seizure or post-

geniculate cortical lesions not causing hallucinatory palinopsia; ** = Cases of prescription drug, illicit

drug, idiopathic, migraine, or head trauma not causing illusory palinopsia; X = Not included in numerical

analysis due to inadequate symptom description or describing non-palinoptic symptoms.

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Dysfunction of Visual Memory Dysfunction of Visual Perception

EtiologyPost-geniculate cortical lesions

Various seizure etiologies, Seizures of

unknown etiology

Patho-physiology

Cortical deafferentation

Focal cortical

irritation

Epileptic discharges

Focal activation of post-geniculate neurons which represent images or

scenes already encoded in visual memory

Type of Palinopsia

Formed image perseveration

Categorical incorporation

Scene perseveration

Patterned visual spread

Symptom Features

High resolution, formed, episodic, not affected by environmental conditions,

lasts more than a few seconds

Associated Symptoms

Complex visual hallucinations, homonymous field deficits

MigraineRx

drugs

Diffuse, persistent neuronal

perceptual abnormalities

Diffuse, persistent neuronal hyperexcitability throughout the visual pathway causing perceptual abnormalities

Diffuse cortical

irritation

Diffuse neurotransmitter or receptor alterations,

GABA/5HT2a?

Cortical spreading depression

HPPDHead

trauma

Focal, transient peak in cortical

activity or excitability

Visual trailing

Light streaking

Prolonged indistinct

afterimages

Variant single image perseveration

Low resolution, persistent, continuous or predictable

Visual snow, halos, oscillopsia, akinetopsia,

entoptic phenomena

Simple visual hallucinations, dysmetropsia, cerebral polyopia, photophobia,

metamorphopsia

Affected by light and motion

Transient, paroxysmal

?

Hallucinatory Palinopsia Illusory palinopsia

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Author/

year Primary Etiology

Palinopsia

Mechanism Diagnostic

Visual Field

Defect Type of Palinopsia Description of Palinopsia Other Visual Sx

Simpson,

2013134

Migraine

cortical spreading

depression

Sx occurred directly after

severe migraine

prolonged

indistinct

afterimages, light

streaking, visual

trails

Bright lights can leave afterimages that persist for

several hours, visual trails. Unformed single color

afterimages when moveing field of vision. Topiramate

resolved migraine sx but did not affect visual sx

phosphenes,

photopsia, visual snow,

photophobia

Sierra-

Hidalgo,

2013132

Topiramate,

zonisamide

diffuse neurotrans-

mitter/receptor Δs

Sx started with drug and

resolved with drug d/c visual trails

Stroboscopic vision for an hour only in AM, objects

moved like agents avoiding bullets in the Matrix.

Increasing frequency so topiramte was d/c. Mild sx

from zonisamide.

Not associated with

migranie or aura

Ziaei,

2013154

Central occiput NHL

irritative hyper-

excitability, edema

CT/FLAIR: signs of

compression, resolved

after chemo

enlarged blind

spot, arcuate

scotoma

categorical

incorporation

Categorical incorporation of church spiral over

buildings, complete resolution after chemotherapy.

Palinopsia was presenting symptom of NHL.

Anabrasan,

20138 Multiple sclerosis

possible MS

demylineation

L tempero-occipital

enhancement; oligoclonal

bands on CSF

variant image

perseveration

Immediate, translucent or black afterimages lasting

seconds to minutes. Improved spontaneously after a

few weeks. Visual sx were MS presentation metamorphopsia

Leo, 201392

HPPD

diffuse neurotrans-

mitter/receptor Δs diagnosis of exclusion

akinetopic visual

trails

Moving objects like "stroboscopic photography"; non-

descript afterimages of objects he had seen previously photopsias

Van der

Stigchel,

2012145

R V1/ thalamic

infarction deafferentation MRI displayed infarctions

L homonymous

field deficit

formed image

perseveration;

light streaks

Formed image perseveration (words) would move to

defective quandrant. Light streaking in defective

quadrant. Closing eyes removed afterimages

Curio,

201238

L occipital

hemangioma

epileptic discharge

irritative hyper-

excitability,

deafferentation

MRI: showed lesion,

resolved with AED

R transient

homonymous VF

deficits

formed image

perseveration

After a cortical hemorrhage, immediate palinopsia for a

few minutes with objects and faces. After 1 week of sx,

started on keppra despite negative EEG and sx

disappeared

Kim, 201280

Carnitine def., 2°

seizure epileptic discharge

Decreased plasma

carnitine, R occipital lesion

formed image

perseveration

After a seizure, noted "persistence of afterimages"

which were vivid and indistinguishable from the real

stimulus Left hemineglect

Evans,

201247

Migraine

cortical spreading

depression

MRI/A unremarkable;

clinical migraine sx which

improved with tx

light streaking,

unknown

Long history of migraines and "constant afterimages" or

tracers, more noticeable in light. Migraine and

palinopsia improved on topiramate

visual snow, blue field

entopic phenomena

Khan,

201177

R parieto-tempero-

occipital GBM

deafferentation,

irritative

hyperexcitability

MRI displayed GBM;

palinopsia resolved after

neoplasm debulking

L homonymous

quadrantanopia

large blind spot

formed image

perseveration

Palinopsia presenting sign of GBM; Delayed palinopsia

of wife or TV in left visual field persisting for about

15minutes. Palinopsia resolved after neoplasm

debulking

Abert,

20101 HPPD

diffuse neurotrans-

mitter/receptor Δs diagnosis of exclusion

akinetopic visual

trails

Described 2 episodes in past 6 months of a "reel of film

in slow motion", perceiving motion as "frame by frame"

Head trauma

diffuse cortical

hyperexcitability

Sx occurred directly after

head trauma

light streaking,

prolonged

indistinct

afterimages

Multiple copies of brightly colored opaque isochromatic

"streamers" near moving bright lights

Trazadone

diffuse neurotrans-

mitter/receptor Δs

Sx disappeared after

trazadone d/c

akinetopic and

blurred visual

trails

6 mo after starting trazadone, c/o stroboscopic vision

and "visual trails" lasting for ~1/2 hr each morning.

Also occurrs during exposure to bright light

HPPD/trazodone

diffuse neurotrans-

mitter/receptor Δs

Sx started over 40 years

ago after LSD use, recent

trazodone use

prolonged

indistinct

afterimages,

akinetopic trails

Motion causes isochromatic, translucent, isointense

distinct trailing images in all fields of gaze. Constant for

40 years after LSD, recently started trazadone.

Metamorphopsia,

halos

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Ossola,

2010115

Seizure of unknown

etiology epileptic discharge

EEG: PLEDS over R parietal

region; Sx resolved with

phenytoin/lorazepam

left

homonymous

field deficit

formed image and

scene

perseveration

Delayed palinopic images and scenes from 30minutes

before, lasting about 30seconds, more often in

hemianopic field. Occurred during end of ictal event CVH

Kataoka,

200975

*

Seizure of unknown

etiology epileptic discharge

EEG: R occipital seizure

discharge; improved with

treatment

non-akinetopic,

discrete visual

trails

Cerebral polyopia w/ unmoving objects, motion would

cause trails and shapes to Δ . Valproate/ gabapentin

resolved polyopia and improved palinopsia

cerebral

polyopia/entomopia

Tsai, 2009144

Posterior corticl

atrophy diffuse atrophy

SPECT: posterior parieto-

occipital hypometabolism

akinetopsia visual

trails

Leftward moving objects were percieved as successive

images side by side. No palinopsia on eye movement

Posterior corticl

atrophy diffuse atrophy MRI: parietal atrophy

akinetopsia visual

trails

Multiple images only when objects moved leftward, not

present on eye movement.

Fontenelle,

200849

Topiramate

diffuse neurotrans-

mitter/receptor Δs

Sx started after topiramate

dose increase

akinetopic visual

trails

Pt c/o stroboscopic vision, images lasted a few sec and

episodes occurred several times a day.

Engelson,

200842

X

POLG1 mutation, 2°

seizure epileptic discharge

POLG1 mutation, R

occipital focus, seizures,

status epilepticus no description No details of the palinopsia were given dysmetropsia

Ritsema,

2007122

L occipital AVM; 2°

seizure

epileptic discharge

irriration

hyperexcitability

Sx after AVM hemorrhage,

during a seizure aura

formed image

perseveration

Immediate formed image perseveration of TV, etc in

defective visual field photopsia

*

L anterior optic

radiation infarction unknown

2 small hyperintensities

within periatrial white

matter

prolonged

indistinct

afterimages

Prolonged indistinct light afterimages, esp when

looking at a white wall. Would also see outline of bright

images such as a lightpost, images would last ~60sec

Kondziella,

200682

R temporo-occipital

GBM unknown

CT showed GBM 5 months

after palinopsia

formed image

perseveration

Delayed palinopsia- wasp in central vision for 2 hrs, CT

originally negative, palinopsia GBM presentation

Mitsuedo-

Ono,

2006107

Seizure of unknown

etiology epileptic discharge

Dx by EEG and clinical

seizure signs; resolved with

AED

scene

perseveration

Seizure episodes lasting about 10seconds occuring

multiple times per day; pt would see a replay of a scene

he had just viewed CVH, cerebral polyopia

Evans,

200646

Topiramate, trazadone

diffuse neurotrans-

mitter/receptor Δs

sx after inc topiramate,

resolved with dose dec visual trails

Multiple afterimages when looking at a moving hand or

person, episodes each morning for about an hr

Topiramate

diffuse neurotrans-

mitter/receptor Δs

sx occurred with dose inc,

resolved with dose dec

visual trails, light

streaking

Shadow images of moving objects or lights, trouble

with night driving. Sx only at night or in dark

Metz, 2006A R occipital infarction

deafferentation,

irritation

hyperactivity

MRI: recent infarction,

clinical sx of CVA

left

homonymous

field deficit

formed image

perseveration

3 days post infarction, patient noted duplicated objects

in her hemianopic field from objects seen in her intact

field. Went away by day 5 SVH, visual allesthesia

Killer,

200578

X

Peduncular

hallucinosis

neurotransmitter

alterations

CT: subcortical

encephalopathy not palinopsia described repetitive visual hallucinations CVH

Abdulfattah,

2005B Migraine

cortical spreading

depression clinical sx of migraine

variant formed

image

perseveration

After a severe migraine, c/o persistence of images in

visual fields for a couple seconds, worse when moving.

Persisted for a few months and slowly resolved.

Sunness,

2004140

HPPD

diffuse neurotrans-

mitter/receptor Δs diagnosis of exclusion

prolonged

indistinct

afterimages

2yr history of prominent fluorescent green afterimages

after viewing bright lights, 1+ year since last LSD use photophobia

Sun, 2004139

TIA

deafferentation,

irritative

hyperexcitability

SPECT: hypoperfusion in R

occipitotemporal region, sx

appeared after TIA

transient L

homonymous

field deficit

scene

perseveration

Immediate palinopsia of waving fingers lasting 3min, in

defective field. This resolved after 1 day and patient

then c/o metamorphopsia for 12 hours

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Smith,

2003135

B-cell NHL, secondary

seizure

epileptic discharge,

irritative

hyperexcitability

palinopsia resolved after

adding carbamazepine to

valproate and chemo

scene

perseveration,

categorical

incorporation

Categorical incorporation with body parts lasting a few

minutes. Repeated scene of a nurse walking. Sx

resolved after adding carbamazepine to valproate.

Symptoms did not return after chemotherapy

cerebral polyopia,

oscillopsia

Gaillard,

200353

HPPD

diffuse neurotrans-

mitter/receptor Δs diagnosis of exclusion

momentary

afterimages

Persistence of an object for several seconds after

shifting gaze onto a white wall

visual snow, blue field

entoptic

HPPD

diffuse neurotrans-

mitter/receptor Δs diagnosis of exclusion dyskinetopsia

Complained of stroboscopic vision (dyskinetopsia) and

difficulty in depth perception decreased stereopsis

Hundal,

200367

Nefazodone

diffuse neurotrans-

mitter/receptor Δs

Sx started after dose

increase

visual trails, light

streaks

Moving objects leave short-lived trails, during fixation,

light adaptation, resolves after 20-30min in bright

conditions

Hayashi,

200261

R parietal hematoma

deafferentation,

irritative hyper-

excitability

Sx occurred after CVA, CT:

subcortical hemorrhage

left

homonymous

field deficit

formed image

perseveration;

scene

perseveratio

Immediate and delayed palinopsia 2-5 days after

hemorrhagic CVA, images (fingers) and scenes

perseverated mostly in the left VF for ~15min. Also

heard examiners voice photopsia

Rubin,

2002124

X Zosuquidar zosuquidar tox no description No details of the palinopsia were given

Idhe-Scholl,

200168

Mirtazepine

diffuse neurotrans-

mitter/receptor Δs

sx occurred with dose inc,

resolved with dose dec visual trails

Saw "visual trails" from moving objects. Less intense

color, slightly blurred, faded after 30sec-1minute.

Worse in lateral visual fields.

Chan,

200133

Posterior corticl

atrophy Diffuse atrophy

MRI: atrophy restricted to

the occipital pole

constricted

peripheral field

patterned visual

spread

After seeing intense color, subsequent objects would

immediately appear in the opposite color for 30-60 sec

Hori, 200064

**

Maprotiline, possible

2° seizure unknown

Maprotiline dec seizure

threshold, pt on other rx

that inc. maprotiline lvl

formed image

persev., patterned

visual spread

Would see perseverated words, pattern on ceiling

spread to arms. Disappeared 1 week after maprotline

d/c

Fournier,

200050

Head trauma

possible diffuse

cortical

hyperexcitability

visal deficits occurred 7+

months after head

trauma/LoC

left

homonymous

field deficit

unidirectional

akinetopic visual

trails

After focusing on an object, would see afterimages

when moving head left like "a strobe light", images

looked real and lasted about 15sec occansional micropsia

Faber,

200048

Nefazodone

diffuse neurotrans-

mitter/receptor Δs

sx started with trazodone,

resolved with dose dec visual trails blur

Pt saw "visual trails of moving objects", same color and

size as original, occured at night or in dim light

Lauterbach,

200088

Trazadone/risperidone

diffuse neurotrans-

mitter/receptor Δs

Sx after dose incr of both

rx, resolved after drug d/c

visual trails and

light streaking

Eminating light from objects and "streamers" would

follow moving objects. Would persist after closing eyes halos around objects

Pomeranz,

2000117

Possible TIA

deafferentation,

irritative

hyperexcitability

patient had stroke 2

months later and a h/o

TIAs

hand motion

only

formed image,

scene

perseveration

2 days after grid laser treatment for diabetic macular

edema, pt saw repeated scenes and images, saw a

woman superimposed on her visual field.

LHON deafferentation

MRI negative; LHON

diagnostic test

nonspecific

vision loss

formed image

perseveration

Shortly after vision loss, pt had immediate palinopsia,

worse when tired or moving. A pink car remained for

30min

Multiple sclerosis

optic neuritis

demylineation

unremarkable

neuroimaging; started after

optic neuritis

variant image

perseveration

Pt saw black and white outlines in same place in VF as

original object, outline of foot. Only with unaffected

eye, improved over time

Idiopathic unknown

unremarkable

neuroimaging

visual trails,

prolonged

indistinct

afterimages

After viewing a bright stimuli, would see isochromatic

afterimages for a few seconds. Motion would cause

trailing

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Idiopathic, possible

migraine

cortical spreading

depression

Possible migraine aura

without headache

visual trails;

prolonged

negative

afterimages

Episodes of scintillating, colored geometric shapes.

After an episode, prolonged physiologic afterimages

worse in AM, changed size based on background

distance, visual trailing; sunglasses helped

oscilliopsia,

phosphenes,

dysmetropsia

Migraine

cortical spreading

depression

unremarkable

neuroimaging sxs started

after migraine type

headache

unknown, variant

image

perseveration?

Daily severe, left throbbing HAs and saw "reduplication

of images". The HA improved but visual sx persisted.

Worse during light adaptation, no improvement from

AED

visual snow, photopsia,

oscillopsia

Vascular

headache/migraine

cortical spreading

depression

unremarkable

neuroimaging sx started

after migraine like

headache

variant image

perseveration

After a throbbing left supraorbital headache, pt

described seeing "several adjacent ghost images".

Delayed image palinopsia with black and white images

visual snow;

phosphenes; cerebral

polyopia

Idiopathic unknown

unremarkable

neuroimaging

visual trails, light

streaking; formed

image

perseveration

Visual trails that lasted a few seconds and merged with

original after motion stopped, looked like original

stimulus, Occurred at night, when fatigued, or after

EtOH. Also saw immediate afterimages on windows phosphenes

Head trauma

diffuse cortical

hyperexcitability

sx started after a bike

accident and orbital

blowout fracture

visual trails,

prolonged

indistinct

afterimages

At night, bright lights would persist in visual field for at

least 1minute. Aso noticed "repetitive echoes of

moving objects"mostly in the AM; wearing sunglasses

helped

Arnold,

199911

*

R parietoccipitl

abscess, Noon-an

syndrome

deafferentation,

irritative

hyperexcitability

palinopsia occurred after

abscess drainage

left

homonymous

heminopsia

variant formed

image

perseveration

Persisting images in defective field similar to original,

lasting several seconds visual allesthesia

Werring,

1999149

L occipital tuberculous

granulomata

irritative

hyperexcitability

resolved after standard

treatment

formed image

perseveration

Persistence of images in his right hemifield. Responded

to standard anti-TB therapy SVH

Kupersmith,

199984;

Pt 2

R parieto-occipital

AVM, 2° seizures

de-afferentation,

epileptic discharge

Angio: DAVM in occipital

lobe, clinical seizure sx,

improved with AED

L homonymous

quadrantanopsia

formed image

perseveration

Images persisted in left lower visual field for up to 30

minutes (cat). Improved with carbemazpine and

completely resolved after embolization scotoma, photopsias

Pt4

R parieto-occipital

AVM de-afferentation Angio: DAVM near torcula

R homonymo-us

VF deficit

categorical

incorporation

Categorical incorporation for faces, body parts. Refused

vascular malformation treatment.

dysmetropsia,

phosphenes

Horton,

199965

Nefazodone

diffuse neurotrans-

mitter/receptor Δs

Sx after dose inc, resolved

with dose decrease

akinetopic visual

trails, light streaks

"Streams of multiple, frozen images trailing in the wake

of moving objects". Images collapsed into real object

after motion. Moving lights created a long comet tail

Nefazodone

diffuse neurotrans-

mitter/receptor Δs

Sx after dose inc, resolved

with dose decrease

akinetopic blurred

visual trails

Visual trails of multiple, blurred images. Occurred with

any moving object and most evident in dim light

Mosberian,

1999108

Nefazodone

diffuse neurotrans-

mitter/receptor Δs

Sx after dose inc, resolved

with dose decrease visual trails

"visual tracking", moving images left visual trails; worse

in AM with insufficient sleep.

Nefazodone

diffuse neurotrans-

mitter/receptor Δs

Sx after dose inc, resolved

with dose decrease light streaks "Stream of lights" behind moving objects

Ogunyumi,

1998113

R occipital cortical

dysplasia epileptic discharge

MRI, EEG = high-amplitude

spikes in right parieto-

occipital region

formed image

perseveration

Had 1 episode of palinopsia seeing houses that he

drove by 5 minutes earlier, palinopic images lasted a

couple minutes

photophobia,

photopsia

Silva,

1997133

seizure of unknown

etiology

epileptic

discharges

Negative EEG and CT head;

sx resolved with

carbamazepine

formed image

perseveration

Started with psychosis and continued after psychosis

ended.Immediate palinopsia for 10sec, the image

would then enlarge, lose shape, and disappear macropsia

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Schwartz,

1997127

Nefazodone

diffuse neurotrans-

mitter/receptor Δs

Sx started after dose

increase visual trails

Patient noticed ghost shadows on moving objects for

~30min after waking, went away after 6 weeks

Vaphadies,

1996146

R occipital infarction deafferentation

MRI: right occipital infarct,

EEG negative

L homonymous

deficit

formed image

perseveration

Saw fragments of objects in defective field that were

recently seen in intact field, lasted 3 days after CVA

X R occipital infarction deafferentation MRI

L homonymous

deficit no description No details of the palinopsia were given phosphenes, CVH

Kawasaki,

199676

HPPD

diffuse neurotrans-

mitter/receptor Δs

Diagnosis of exclusion,

occurred after wisdom

tooth extraction

prolonged

physiological

afterimages

4 mo after LSD use, received fentanyl, methohexital,

midazolam, dexamethasone, and lidocaine for a

surgery. Prolonged physiologic afterimages, more vivid

in bright lights. No resolution in 3+ yrs

HPPD

diffuse neurotrans-

mitter/receptor Δs diagnosis of exclusion

prolonged

physiological

afterimages

2 mo after LSD ingestion, negative afterimages more

prominent with high contrast, lasted up to 1 min.

Precipitated by hot baths photopsia, phosphenes

HPPD

diffuse neurotrans-

mitter/receptor Δs diagnosis of exclusion visual trails

Pt noted a "series of images that trailed behind the

moving object for a few seconds". Occurred with any

object in motion, constant, unchanged after 6mo

Kraus,

199683

Nefazodone

diffuse neurotrans-

mitter/receptor Δs

Sx after dose inc, resolved

with dose decrease

visual trails, light

streaks

Visual trails from moving objects lasting ~1sec, more

apparent at night, occur when turning her head

Abraham,

19965 HPPD/risperidone

diffuse neurotrans-

mitter/receptor Δs

sx in close proximity to

risperidone dose increase visual trails

Pt used LSD ~35 times, had HPPD visual trailing. Panic

attacks and worse flashbacks after risperidone

HPPD/risperidone

diffuse neurotrans-

mitter/receptor Δs

started in close proximity

as risperidone initiation visual trails

Continuous visual symptoms of non-descript

"afterimages", visual trails, and halos. Worsened after

starting risperidone which also caused a panic attack halos

HPPD/risperidone

diffuse neurotrans-

mitter/receptor Δs

started in close proximity

as risperidone initiation

visual trails,

prolonged

indistinct

afterimages

A week after his last LSD trip, pt experienced visual

trails and intensification/prolongation of light. Many

years later, respiradone caused flashbacks/panic

attacks intensification of light

Muller,

1995111

R occipital infarction,

2° seizure

epileptic discharge,

deafferentation

EEG during palinopsia: Δ

focus with sharp waves in R

temporal area; resolved

with phenytoin

left

homonymous

field deficit

formed image

perseveration

Immediate and delayed palinopsia of faces and other

scenic after-images. No other signs of seizure.

R occipitotemp-oral

mets, 2° seizure

epileptic discharge,

deafferentation

EEG= R sharp waves;

resolved with AED

left

homonymous

field deficit

formed image

perseveration

Pt saw images of delayed palinopic images of people

from minutes before.

R occipitotemp-oral

mets, 2° seizure

epileptic discharge,

deafferentation

EEG: R occipitotemporal

delta focus, paroxysmal

bilateral theta/delta

waves; resolved with AED

left

homonymous

field deficit

scene

perseveration

For weeks, patient reported complete visual scenes

from seconds or minutes before such as a soccer player

throwing a ball in his hemianopic field.

Purvin,

1995120

Clomiphene

diffuse neurotrans-

mitter/receptor Δs

Palinopsia occurred after

clomiphene dose increase visual trails

Noticed prolongation of afterimages of moving targets.

Worse in high-contrast images in bright light. Visual

disturbance never abated

shimmering,

oscillopsia,

photophobia

Clomiphene

diffuse neurotrans-

mitter/receptor Δs

after clomiphene dose

increase visual trails?

4 mo after starting clomiphene, "abnormal

prolongation of afterimages" for moving objects; worse

after entering bright room, not resolved 4 years later

shimmering,oscillopsia,

photophobia

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Clomiphene

diffuse neurotrans-

mitter/receptor Δs

Palinopsia occurred after

clomiphene dose increase visual trails

Pt described stroboscopic vision. Symptoms worsened

during light adaptation and during menses, persisted

for 7 years after d/c clomiphene

blurred vision,

photophobia, visual

snow

Liu, 199596

X

Head trauma,

migraine

diffuse cortical

hyperexcitability

clinical diagnosis, SPECT:

biparietal hypoperfusion no description

After a MVA, developed a persistence of afterimages.

Resolved with nortryptaline and carbamazepine visual snow

McGuire,

1994102

X MDMA

diffuse neurotrans-

mitter/receptor Δs diagnosis of exclusion no description No details of the palinopsia were given

Marnenos,

1993100

Schizophrenia unknown

started with schizophrenia

onset, worsened before

psychosis

formed image

perseveration;

visual trails

Immediate and delayed afterimages, same size, shape,

and color. Visual trails with eye movement. Palinopsia

worsening when tired, stressed, or before psychotic

episode; lasted for 5+ years

CVH, photopsia,

teleopsia, oscillopsia

Gottlieb,

199257

*

Infarctions post-CABG,

largest R parietal deafferentation

CT: multiple infarctions;

normal EEG

left

homonymous

field deficit

unidirectional

visual trails eye

scanning

Palinopsia induced by leftward horizontal scanning of

an objects, lasting 5-10 seconds. Increasing the contrast

made it worse; misdiagnosed as polyopia micropsia

Lunardi,

199198

L occipital abscess,

Kartagener's

syndrome

deafferentation,

irritative

hyperactivity

edema

CT: left occipital abscess

with perilesional edema;

resolved with drainage

R homonymous

quadrantanopsia

categorical

incorporation

1 episode of categorical incorporation with faces and

clothes lasting 10mintes, went away after abscess

drainage

Friedman,

199151

X IL-2 unknown

unremarkable

neuroimaging (CT) no description

"persistent image overlapping the true image lasting

several minutes", began 11 days after IL-2 scintillating scotoma

Levi, 199094

pt2 HPPD

diffuse neurotrans-

mitter/receptor Δs diagnosis of exclusion

akinetopsia visual

trails

Moving objects a series of still pictures, episodes last

~1hr, multiple times/day. Precipitated by stress or by

describing phenomenon to others, lasted 1+ years decreased stereopsis

pt4 HPPD

diffuse neurotrans-

mitter/receptor Δs diagnosis of exclusion

light streaking;

formed image

perseveration

2 yrs after last drug use, moving lights in dark appeared

as streaks; After looking at an object, a life-like image

stayed for secs to mins, even after closing eyes

pt6 HPPD

diffuse neurotrans-

mitter/receptor Δs diagnosis of exclusion

light streaking,

visual trails

During a stressful period, noticed streaking of moving

objects, did not occur if tracking object with eyes.

Worse with bright objects in dark settings.

Hughes,

199066

** Trazadone

diffuse neurotrans-

mitter/receptor Δs

Sx after dose inc, resolved

with dose decrease

formed image

perseveration

Immediate palinopsia, worse in temporal fields, lasting

up to 15min. She or the object (door, crib) had to be

moving. Only in the morning, frequent, intense

Trazadone

diffuse neurotrans-

mitter/receptor Δs

MRI: 1.5cm frontal lobe

meningioma; palinopsia

resolved with rx d/c

akinetopic visual

trails

Saw "strobelike afterimages" of objects in motion.

Worse in peripheral visual fields and with insufficient

sleep.

Trazadone

diffuse neurotrans-

mitter/receptor Δs

Sx after dose inc, resolved

with dose decrease

akinetopic visual

trails

Strobe images in AM. After fixating on a door and

moving his gaze, he would see multiple images of the

door "march" across the room. Episodes lasted 15mins

Purvin,

1989119

Creutzfeld-Jacob

disease

deafferentation,

possible epileptic

discharge

Unremarkable

neuroimaging; EEG:

marked slowing, periodic

sharp wave discharges;

L and R

homonymous VF

deficits

formed image

perseveration;

categorical

incorporation

Immediate palinopsia with mustard label, palinopsia

would last for a few minutes up to an hour, anywhere

in his visual field. Categorical incorporation with

houses. Presenting symptom of CJD photopsia

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Young,

1989152

R parietal astrocytoma

epileptic

discharges

EEG: PLEDs in R parietal

region, resolved with AED

formed image

perseveration;

categorical

incorporation

Immediate palinopsia in her left field. Categorical

incorporation with beards, eyes. Palinopsia was

presenting symptom of neoplasm

CVH, cerebral

polyopia,

dyschromotopsia,

dysmetropsia,

metamorphosia

Lefebre,

198991

R parieto-occipital

astrocytoma

epileptic discharge,

deafferentation

EEG: pt noticed palinopsia

1s after first sharp wave in

R temperoparietal region

upper left

quadrantanopsia

formed image

perseveration;

categorical

incorporation

6 mo after astrocytoma debulking, immediate and

delayed palinopsia in VF deficit. Images lasted secs to

hrs, sometimes translucent, stayed with eye closure.

Categorical incorporation of taxi sign onto other cars.

Johnson,

198872

Hyperglycemia, 2°

seizure

epileptic discharge;

deafferentation

EEG: L occipital focus,

seizure sx; resolved after

glucose normalized

right

homonymous

field deficit

formed image

perseveration

Had spells that included seizure sx, SVH, and immediate

palinopsia with formed images SVH, visual allesthesia

Gates,

198856

X Depression

neurotransmitter

alterations

CT: large left occipital lobe

infarction

R homonymo-us

VF deficit not palinopsia

Pt. with psychosis had repetitive episodes of

"hallucinated" pac-man moving towards VF deficit SVH

Ardila,

198710

L occipital

neurocysticercosis

cyst

epileptic discharge

irriration hyper-

excitability,

deafferentation

palinopsia started 1 day

after GTC, resolved with

anti-epileptic

transient right

homonymous

field deficit

scene

perseveration

During tx for neurocysticorcosis, had a GTC seizure and

afterwards had scene perseveration of orderly bringing

tray into the room with same speed, color, shape,

lasted about 30min in right visual field.

visual allesthesia,

cerebral polyopia, SVH

R occipital infarction

deafferentation;

irritation

hyperexcitability CT: right occipital infarction

left

homonymous

field deficit

scene and variant

formed image

perseveration

Long history of vascular headaches with momentary

image perseveration; after a CVA, got neuro signs, VF

deficits, and scene perseveration

dysmetropsia,

proposagnosia,

oscillopsia

Blythe,

198620

Idiopathic

rheumatological

disease unknown

unremarkable

neuroimaging, high ESR, sx

started while pregnant;

mildly improved on

carbamazepine

prolonged

indistinct

afterimages, light

streaking

After an unclear rheumatologic/neurologic insults, pt

noticed positive prolonged light afterimages, light

streaking. Worse for high contrast images, continuous,

depedent on brightness and stimulus exposure length.

Flash of camera would last 10-20minutes.

visual snow,

photophobia

Landis,

198686

R occipito-parietal

infarction

deafferentation,

irritation

hyperexcitability

CT: R occipitotemporal

infarction, EEG: slow wave

activity in R posterior

temporal region

left

homonymous

field deficit

categorical

incorporation,

scene

perseveration

Categorical incorporation with dog face. Repeated

scene of man walking. Palinopsia worsened over next

10 months

CVH, metamorphopsia,

prosopagnosia,

photopsia

Joseph,

198674

X Capgras and Cotard

syndrome of

subjective doubles unknown not palinopsia

Overtly psychotic man would look in mirror and see

two images of himself, one he dubbed an imposter CVH

Jacome,

198571

Multiple sclerosis

unknown/possible

MS demylineation

neuroimaging

unremarkable; VEP:

probable bilateral

retrochiasmal optic neuritis

bitemporal

visual extinction

on fixation

prolonged

indistinct

afterimages, light

streaking, variant

formed image

perseveration

After fixation, black images would momentarily appear

in her temporal visual fields seconds to minutes after

seeing object. Bright lights persisted for several hours;

images removed with head shaking or blinking

bilateral INO,

photophobia,

photopsia

Patterson,

1985116

R occipital abcess,

AML deafferentation

CT showed abscess and

autopsy, palinopsia was

presenting sx

left

homonymous

field deficit

categorical

incorporation

formed image

perseveratn

Severe headache then categorical incorporation with

boots on TV; delayed image perseveration with an

elephant on a billboard; palinopsia occurred over 10

days blurry vision

Lang, 198587

L occipital infarction deafferentation

CT: showed infarction,

palinopsia started after

right

homonymous

field deficit

formed image

perseveration

After a heart attack and a subsequent CVA, patient

noticed perseverated, moving letters to the point that

he could not read; resolved after 4 months

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Bynke,

198430

R temporal glioma

deafferentation,

irritative

hyperexcitability

CT: glioma, palinopsia after

tumor debulking

L homonymous

field deficit

formed image

perseveration

For weeks after operations, would see objects (red

roses) stationary in visual field for 10minutes.

Lazaro,

198389

R occipital GBM deafferentation

CT showed GBM;

presented as palinopsia

left

homonymous

field deficit

categorical

incorporation

1 episode of categorical incorporation with people,

lasting several minutes. Palinopsia was part of

presentation of GBM

transient visual

obscurations,

metamorphopsia

Cummings,

198237

R parieto-occipital

gliosis

irritation

hyperexcitability,

deafferentation

palinopsia started

immediately after surgery,

unaffected by phenyyoin

left

homonymous

field deficit

formed image

perseveration

After fixation, image persisted for 30-90 secs, worse

during high contrast; immediate or delayed, also

occured based on thought; daily for 6 years

micropsia, simple

visual hallucinations

Eretto,

198245

R occipital AVM, 2°

seizure

epileptic discharge

irritative

hyperexcitability

palinopsia started after

surgery, improved with

anti-epileptic

formed image

perseveration

Patient reports seeing a negative afterimage for a few

seconds, then the image jumped to the opposite VF

and turned positive, new image lasted a few minutes

macropsia, visual

allesthesia

Cleland,

198135

R parietal infarction

epileptic discharge,

deafferentation

CT: Right post. parietal

infarction, EEG: right

temporal abnormality

L homonymo-us

quadrant-

anopsia

scene

perseveration

Saw action of man walk in left VF repeated at twice the

speed for ~10min. Similar symptoms with a child

waving and brother putting hand in hair vision misty

Michel,

1980106

R occipital infarction,

maybe tumor deafferentation

CT: dec density in R

occipital lobe, no EEG;

asymptomatic after

radiation

subtle left

homonymous

deficit

patterned visual

spread,

categorical

incorporation

Cateogorical incorporation with faces, clothes, money.

patterned visual spread with a banana all over a wall

and a $20 bill

Hyperglycemia, 2°

seizure

epileptic discharge,

deafferentation

CT showed infarction;

palinopsia resolved after

glucose normalization

congruous left

homonymous

field deficit

formed image

perseveration;

categorical

incorporation

After looking at a picture, it persisted in left field of

vision. Categorical incorporation with faces. Blood

sugar was 534 when admitted to hospital

L occipital infarction

deafferentation,

irritation

hyperactivity

CT showed infarction, only

episode close proximity

after CVA

right

homonymous

field deficit

formed image

perseveration

After seeing objects on the table, he would look away

but still saw the objects floating in space, thought

palinopic images were real. Only had 1 episode

Jacobs,

198069

R parieto-occipital

AVM, 2° seizures

epileptic discharge,

irritative

hyperexcitability

angiogram: AVM; EEG:

right parietoccipital focus,

clinical seizure sx, resolved

with AED

formed image

perseveration

Immediate and delayed palinopsia 2 weeks after

neurosurgical procedure, objects would remain 3-

15minutes after stimulus was removed, the palinoptic

would be smaller and oscillate vertically

left homonymous

hemichromatopsia,

visual allesthesia

Swash,

1979141

Seizure of unknown

etiology epileptic discharge

EEG: episodic theta activity

in L temporal area; clinical

sx of seizure

formed image

perseveration

Patient would stare blankly into space for a few

seconds and have immediate afterimages that

persisted for several minutes

X

seizure of unknown

etiology epileptic discharge

CT negative; EEG:

sharpened theta wave

activity on the left not palinopsia

3 yr h/o seizures where his whole visual field would

remain fixed for several minutes until slowly fading

away; attacks stopped after phenytoin treatment

Meadows,

1977104

R occipitotemporal

infarction

deafferentation;

irritatiive

hyperexcitability

right occipitotemporal

infarct on autopsy

homonymous

left upper

quadrantanopsia

formed image

perseveration;

patterned visual

spread,

categorical

incorporation

categorical incoporation with beards superimposed on

people, delayed afterimage of candle; died a week later

from infarction

R occipitotemporal

meningioma, 2°

seizure epileptic discharge

Sx started with d/c of AED

and resolved by restarting

the AED

left

homonymous

field deficit

formed image

perseveration

Delayed palinopsia after stopping phenyyoin, saw

husbands face and a window in her defective visual

field CVH

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** Idiopathic deafferentation normal EEG, Tc brain scan

L homonynous

quadrantanopsia

formed image

perseveration

1 episode of delayed palinopsia with barley lasting for 5

minutes

Brust,

197725

Hyperglcyemia, 2°

seizures

epileptic discharge

irritative

hyperexcitability

EEG: R occipitotemporal

spikes, Sx resolved with

glucose normalization and

AEDs

transient left

homonymous

field deficit

formed image

perseveration;

scene

perseveration

Patient with 390-700mg/dL blood sugars would have

seizures. After ictal activity, he would get transient

scotomas in left VF and see images or scenes in the

scotoma that he saw minutes to years before.

phosphenes,

metamorphopsia,

faces "melt"

Lance,

197685

pt 7 R occipital infarction

deafferentation;

irritative

hyperexcitability

Tc scan: R occipital

infarction; palinopsia

occurred after CVA

left

homonymous

field deficit

scene

perseveration

After seeing a man walk past on his left side, would see

the repetition of the scene in VF deficit

dysmetropsia,

metamorphopsia, CVH,

cerebral polyopia

pt 9

R occipital infarction,

2° seizure

epileptic discharge,

deafferentation

Palinopsia resolved after

AED

left

homonymous

field deficit

scene

perseveration;

formed image

perseveration

4 months after an occipital lobe infarction, saw

repeated scenes of people walking on both sides (visual

allesthesia), often in VF deficit

simple and CVH,

metamorphopsia

Anderson,

19729 HPPD

diffuse neurotrans-

mitter/receptor Δs

diagnosis of exclusion;

resolved with

trifluoperazine

akintopsia visual

trails

After ~65 hallucinogen doses in previous month, pt saw

motion as stroboscopic vision. Described it as constant,

worsened by light and concentration

photopsia, SVH,

depersonalization

Bender,

196817

pt 1

R posterior

hemisphere

metastasis deafferentation

angiogram: R occipital

lesion, palinopsia resolved

as VFD enlarged

left

homonymous

field deficit

formed image

perseveration

Delayed palinopsia of objects seen in recent past (clock,

eyes) in left VF lasting a few minutes, usually in same

location, persisted after eye closure

dysmetropsia, SVH,

visual allesthesia

pt 2

R occipital

meningioma

epileptic discharge,

deafferentation

angiogram: right occipital

meningioma, clinical sx of

seizure

L homonymous

quadrantanopsia

formed image

perseveration,

prolonged

indistinct

afterimages

"Shimmering of images" and seizures with intermittant

palinopic images in VF deficit for 4 years. Palinopsia

progressively worsened in frequency, length, and

became more delayed (30sec to eventually 30minutes)

dysmetropsia,

metamorphopsia,

cerebral polyopia

pt 3

R parieto-occipital

glioma

epileptic discharge,

deafferentation

angiogram: right parieto-

occipital glioma, clinical sx

of seizure

left

homonymous

field deficit

formed image

perseveration,

categorical

incorporation

Palinopic letters, zebra, hands in left visual field. False

images lasted 10-15seconds and would disppear and

re-appear over 20minutes, palinoptic images occurred

only at presentation of tumor

pt 4

Seizure of unknown

etiology

epileptic discharge,

deafferentation

normal angiogram, EEG:

bilateral occipito-temporal

spikes

transient,

homonymous

field deficits

formed image

perseveration

Patient not oriented to time/place. Stationary, fixed

palinopic images lasting a few minutes, not specific to a

part of visual field. Occurred with transient visual field

deficits and with eyelids opened or closed.

cerebral polyopia,

dysmetropsia, CVH,

achromotopsia,

metamorphopsia

pt 10

L parietal

ependymoma, 2°

seizures

epileptic discharge

irritation

hyperexcitability

Angiography, biopsy,

clinical seizure sx

formed image

perseveration

Two months after operation for neoplasm removal,

noticed enlarged perseverated images; also noticed

ringing in ears at same time macropsia

pt 11

R occipital lobe

aneursym

deafferentation,

irritation

hyperexcitability

Palinopsia occurred after

procedure to treat

aneursym

left

homonymous

field deficit

formed image

perseveration

For two years after operation, had photopsia and

immediate palinopsia in left visual field with

afterimages lasting about 1 minute SVH

pt 5-9, 12 no description Did not adequately describe symptom or etiology