Palinopsia is a pathological visual phenomenon in which an image persists or recurs after the visual stimulus has been removed. The term originates from the Greek words palin (again) and opsia (seeing). Unlike physiological afterimages, it tends to last longer and be more vivid. While physiological afterimages appear briefly as complementary colors (negative afterimages), palinopsia appears in the same color as the original stimulus (positive afterimage) and may occur immediately or after a delay.
Historically, Critchley (1951) described “paliopsia” and “illusory visual spread,” and later Kölmel classified it into three types: immediate palinopsia, true palinopsia (minutes to hours), and hallucinatory palinopsia (days to weeks). 4)
Two major categories are hallucinatory palinopsia and illusory palinopsia.
Epidemiology: Large-scale data are limited. It may occur in up to 10% of migraine patients, and is more frequent in migraine with aura.
Physiological afterimages disappear soon after stimulus removal, appear in complementary colors (opposite to the original stimulus), and are a normal response. Palinopsia is a pathological phenomenon that lasts longer, appears in the same color as the original stimulus (positive afterimage), and may appear with a delay after the stimulus, requiring investigation for underlying disease.
The differences in symptoms between type 2 are shown below.
Hallucinatory Polyopia
Duration: Several minutes to several hours (may extend to several days or weeks).
Resolution: High resolution and vivid.
Appearance pattern: Appears anywhere in the visual field. Not affected by environment (light, movement).
Content: Previously seen images or scenes appear as complex visual hallucinations. Often causes significant stress to the patient. 1)
Illusory Palinopsia
Duration: Short (appears immediately after stimulus).
Resolution: Low resolution, unclear.
Appearance pattern: Influenced by background contrast, stimulus intensity, and ambient lighting. 2)
Content: Distortion of real external stimuli. The shape, color, or size of the image is perceived as changed.
Related symptoms that may occur include photopsia, metamorphopsia, visual snow, oscillopsia, entoptic phenomena, and cerebral polyopia.
In hallucinatory palinopsia associated with normal pressure hydrocephalus (NPH), recurrence of images persisting for 1–3 seconds after stimulus removal coexists with gait disturbance, cognitive impairment, and urinary incontinence. 1)
In drug-induced palinopsia due to the CDK4/6 inhibitor ribociclib, a characteristic temporal correlation is observed: it appears during the dosing period (days 1–21) and disappears during the drug-free period (1 week). 2)
Causes are divided into two types based on the mechanism of onset.
| Type | Main cause |
|---|---|
| Hallucinatory | Occipital lobe lesions (tumor, infarction, tuberculoma), epilepsy, normal pressure hydrocephalus, CNS demyelination |
| Illusory | Migraine, HPPD, head trauma, drug-induced, idiopathic |
Causes of hallucinatory palinopsia include lesions of the occipitoparietal cortex (tumor, infarction, hemorrhage, arteriovenous malformation, abscess, tuberculoma), epileptic seizures (including those related to hyperglycemia, carnitine deficiency, ion channel abnormalities, and metabolic abnormalities associated with Creutzfeldt-Jakob disease), normal pressure hydrocephalus (presumed mechanism: compression of the posterior visual pathways due to ventricular enlargement)1), and CNS demyelinating diseases.
Causes of illusory palinopsia include migraine (changes in neurotransmitter receptors), hallucinogen persisting perception disorder (HPPD), head trauma, drug-induced causes (trazodone, nefazodone, mirtazapine, topiramate, clomiphene, oral contraceptives, risperidone), the CDK4/6 inhibitor ribociclib2), and idiopathic causes.
Risk factors include a history of migraine with aura and the use of medications that affect the serotonin system.
Medications reported to cause illusory palinopsia include trazodone, nefazodone, mirtazapine (antidepressants), topiramate (antiepileptic), risperidone (antipsychotic), clomiphene, and oral contraceptives (hormonal drugs). Recently, two cases of palinopsia due to the CDK4/6 inhibitor ribociclib have also been reported2), making it important to check current medications for diagnosis.
The diagnosis of palinopsia is made clinically. There is no specific diagnostic test. A thorough ophthalmological and neurological history and physical examination are fundamental, and the interview determines whether it is hallucinatory or illusory (checking duration, environmental dependence, and image resolution).
Neuroimaging (MRI): Essential for hallucinatory palinopsia to search for structural lesions in the posterior visual pathway.
Diagnosis is made by brain MRI/CT. Correlating visual field and associated neurological symptoms with neuroimaging is useful for precise estimation of the lesion location.
Automated perimetry: Checks for visual field defects. In the tuberculoma case, a homonymous left superior central scotoma was observed. 3)
Electroencephalography (EEG): Investigates association with epileptic seizures. In the tuberculoma case, focal epileptic discharges were confirmed during visual hallucinations. 3) In illusory palinopsia without structural abnormalities, epileptiform discharges are often absent.
Optical coherence tomography (OCT): In drug-induced palinopsia, the retinal nerve fiber layer (RNFL), macula, and ganglion cell layer were all normal. 2)
Differential diagnosis includes the following:
In hallucinatory palinopsia, it is essential to rule out structural lesions of the posterior visual pathway (tumor, infarction, tuberculoma, etc.), and MRI is strongly recommended. In contrast, for illusory palinopsia, clinical judgment is used. In both cases, differentiation from psychiatric disorders is important, and the presence or absence of insight and auditory hallucinations should be confirmed through history taking.
Treatment is primarily based on addressing the underlying cause.
Medications that reduce neuronal excitability are an option. However, evidence is limited to case reports, and further research is needed.
Clonidine, gabapentin, acetazolamide, magnesium, and calcium channel blockers are used, but efficacy varies across reports, and established evidence is limited. If drug-induced, improvement can be expected with discontinuation or dose reduction of the causative drug. 2)
Type 2 arises through different mechanisms.
Pathophysiology of hallucinatory palinopsia: It results from dysfunction of visual memory. Mechanisms include cortical deafferentation, local cortical stimulation, and epileptic discharges. Local cortical hyperexcitability or hyperactivity of the posterior visual pathway is considered the final common pathway. Visual perseveration is more common with right parieto-occipital lesions.
Pathophysiology of illusory palinopsia: It results from dysfunction of visual perception, with changes in neuronal excitability in the visual pathway being the central mechanism.
Involvement of the 5-HT2 receptor has been suggested. Drugs that cause palinopsia (trazodone, nefazodone, risperidone, mirtazapine) are 5-HT2 receptor antagonists, while LSD is a 5-HT2A/5-HT2C agonist, and it is presumed that excitotoxicity of the 5-HT2 receptor is involved.
As a presumed mechanism of palinopsia due to CDK4/6 inhibitors, it has been reported that CDK4/6 inhibitors are not cell-specific and may interfere with the cell cycle of normal cells in brain tissue, and that estrogen interacts with cholinergic and serotonergic systems, and hormone therapy may interfere with CNS processes involved in vision. 2)
In illusory visual spread in frontotemporal lobar degeneration (FTD), dysfunction of the parietal coordination system, abnormalities in feedback pathways for light and motion processing, and compensatory hyperactivation of the right hemisphere due to left hemisphere hypofunction (diaschisis) have been proposed. 4)
Martos et al. (2024) reported two cases of palinopsia that developed during ribociclib plus letrozole therapy used as first-line treatment for metastatic breast cancer. In both cases, it appeared in a time- and dose-dependent manner, disappeared during a drug holiday (1 week), and was manageable with dose reduction to 400 mg. It is suggested that with the widespread use of ribociclib, this may become a not uncommon complication. 2)
Ferguson & Snavely (2024) reported the first case in the literature of palinopsia associated with normal pressure hydrocephalus (NPH). The presumed mechanism is compression of the posterior visual pathways due to ventricular enlargement, and after VP shunting, sustained improvement in palinopsia, gait disturbance, and cognitive impairment was observed at 6 months. 1)
Hoffmann (2021) reported hypervisual illusory spread in non-fluent aphasia plus behavioral variant FTD and proposed it as a new visual environmental dependency syndrome belonging to the palinopsia spectrum. Mechanisms involving parietal lobe dysfunction and diaschisis have been suggested. 4)
Palinopsia is also positioned as one of the additional visual symptoms of Visual Snow Syndrome (VSS), but the pathophysiology and treatment of VSS itself are currently not established.
