Palinopsia is the persistence or recurrence of visual images after the initial stimulus has been removed and is believed to be caused by failure to suppress after images (1,2). It may be due to dysfunction of the coordinate systems of the parietal lobes (3). Typical symptoms of palinopsia include echoing, ghosting, multiple images, smearing, streaming, trailing, or vibrating of the initial image.
Palinopsia may occur in otherwise normal patients (4) or those with migraine (5), epilepsy (6), mitochondrial disease (7), diseases affecting parieto–occipital pathways (8), multiple sclerosis (9), non-Hodgkin's lymphoma (10), stroke (11), glioma (12) metabolic disorders (carbon monoxide poisoning  and nonketatic hyperglycemia ), drugs including marijuana (15), mescaline (16), lysergic acid diethylamide (LSD) (17), methylenedioxymethamphetamine (MDMA) (18), interleukin (19), trazodone (20), zonisamide (4), nefazodone (21), clomiphene (22), and topiramate (23–25).
Topiramate is an antiepileptic drug with multiple mechanisms of action including: 1) blocking the repetitive action of sodium channels and L-type calcium channels, 2) potentiating gamma-aminobutyric acid inhibition, 3) modulating glutamate receptors, and 4) inhibiting carbonic anhydrase (26,27). It is frequently used to treat epilepsy, migraine prophylaxis (28), and, occasionally, for idiopathic intracranial hypertension (29).
Common side effects of topiramate therapy include paresthesia, fatigue, anxiety, cognitive impairment, and dizziness (27). Ocular side effects include increasing myopia and angle closure glaucoma (30).
We report 9 cases of topiramate-induced palinopsia (Table 1) and present 3 illustrative cases.
A 42-year-old woman with history of migraine since adolescence, on topiramate for about a year, complained of “tracer vision.” She reported that after moving her arm, she continued to see images of the arm moving for a few seconds. The images were noticeable particularly with movement of her arms but not with movement of her legs or other objects. Her symptoms were worse in the morning and improved later in the day. The symptoms improved, but did not resolve completely, after stopping topiramate.
She had no history of seizures, significant head injury, or illicit drug use. She had taken trazodone for many years but did not develop palinopsia until on topiramate. Magnetic resonance imaging (MRI) of the brain was normal.
A 40-year-old woman presented with a diagnosis of migraine without aura and history of a pretectal glioma. She had tried multiple medications to control headache including tricyclic antidepressants, beta-blockers, ergotamine, antiepileptics, calcium-channel blockers, nonsteroidal anti-inflammatory medications, triptans, serotonin receptor inhibitors, muscle relaxants, narcotics, steroids, benzodiazepines, and neuroleptics. She developed palinopsia when she was prescribed topiramate, 200 mg daily. She reported that objects left a trail as in cartoons and persistence of an image when she looked away from it. In addition to palinopsia, she complained of poor concentration and memory and word-finding difficulty. At her 5 years follow-up appointment, she reported significant improvement of symptoms, although she was still taking topiramate 100 mg daily.
A 58-year-old woman with history of left frontal meningioma and migraine presented with palinopsia. After her topiramate dose was increased from 50 mg twice a day to 3 times a day, she reported seeing “multiple snap shots” of hands as from the movie “Look Who's Talking.” This occurred every other day, most notably early in the morning after awakening from sleep. Once the dose of topiramate was decreased to 50 mg twice a day, her palinopsia resolved. Brain MRI showed a left frontal meningioma that was unchanged from previous scans.
Our 9 patients and the 4 patients previously reported developed palinopsia while on topiramate. All patients were women, 76.9% had migraine, 15.4% had idiopathic intracranial hypertension, and 7.7% had bulimia nervosa (Table 1). The preponderance of women in our series is likely due to the fact that the associated disorders are more common in women. The lowest dose of topiramate that caused palinopsia was 25 mg twice a day. Symptoms resolved in 8 patients after stopping or reducing the medication. More than half of our patients had palinopsia in early morning or late evening. We do not have an explanation for this finding.
Topiramate, like other systemic drugs that induce palinopsia, may inhibit neural activity. Palinopsia may occur in patients with a predisposition to decreased speed of visual processing with additional decreased neural activity from a central nervous system suppressant such as topiramate. Alternatively, Dubois and Vanrullen (31) proposed failure of motion streak suppression as a possible mechanism of palinopsia.
Topiramate affects sodium and calcium ion channels, impairs glutamate transmission and carbonic anhydrase function, and also potentiates gamma-aminobutyric acid inhibition (26,27). The pathophysiology of palinopsia has been proposed to be an increase in serotonergic activity secondary to 5-HT2 receptors. Several drugs associated with palinopsia affect 5-HT2 receptor including LSD, MDMA, nefazodone, trazodone, risperidone, zonisamide, and mirtazapine (18,23,25,32). Weight loss seen in patients on topiramate also may be secondary to 5-HT2c receptor activation (16,33). Topiramate also inhibits CYPD6 gene (34), which may precipitate the serotonin syndrome (35).
Some of our patients presented with potential confounding risk factors for developing palinopsia. Case 1 was on trazodone chronically. Although the patient developed palinopsia only after starting on topiramate, trazodone may have potentiated the effect of topiramate. Case 9 also had taken trazodone before starting topiramate, but with symptoms again developing only after starting topiramate. Seven patients also had migraine as a potential confounding factor.
In 8 of 9 patients, symptoms either improved after decreasing the dose or resolved after lowering the dose or stopping topiramate. Two patients (Cases 2 and 5) preferred to stay on topiramate to control their headache despite persistent palinopsia. In one patient, palinopsia did not resolve after stopping the medication, perhaps because of use of trazodone.
The time between starting topiramate and onset of palinopsia could not accurately be documented. In most cases, the time course was either omitted or described as “briefly” or “soon after.” In Case 4, the time of onset was documented as 3 months after starting the medication.
Topiramate-induced palinopsia is likely uncommon considering how often the medication is prescribed. However, it may go unrecognized because patients may not report the symptom, unless specifically asked for by the clinician.
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