Clinical manifestations

Presentation and course

The following are the published criteria for the clinical definition of visual snow syndrome (42; 38):

The main symptom in visual snow, common to all patients with and without the full syndrome, is the visual static (described in criterion A). The moving dots that constitute the static are typically of black/grey color on a white background and of grey/white color on a black background; they can, however, also be transparent, white flashing, or multicolored. A single patient can present more than one type of static color, with some subjects experiencing all four types in different moments. Of the combinations, black and white static associated with transparent static seems to be the most common (37).

About three quarters of individuals with visual snow report at least three of four accompanying visual phenomena (criterion B), in addition to the static. These symptoms, that as specified constitute the visual snow syndrome, are: palinopsia, exaggerated entoptic phenomena, photophobia, and nyctalopia.

Palinopsia is a neurologic phenomenon described as the persistence of an image even after the originating stimulus has disappeared from the visual field (11). In visual snow syndrome palinopsia typically manifests as afterimages or as visual trailing. The afterimage of visual snow is different from a typical retinal afterimage that occurs when staring at a high contrast image and is perceived in complementary color (24); this phenomenon can be experienced by healthy individuals.

Entoptic phenomena are symptoms that arise from the optic apparatus and that are often normally perceived in the general population. In visual snow, however, they are present on a daily basis, becoming very debilitating and causing disruption in normal vision. Visual snow entoptic phenomena can include excessive floaters in both eyes, excessive blue field entoptic phenomena (uncountable little grey/white/black dots or rings shooting over the visual field of both eyes when looking at homogeneous bright surfaces such as the blue sky), self-light of the eye (colored waves or clouds perceived when closing the eyes in the dark), and spontaneous photopsia, characterized by bright flashes of light.

Nearly two thirds of individuals with visual snow report light sensitivity. The key characteristic of photophobia is the avoidance of light, which can either be perceived as being too bright (photic hypersensitivity) or in some cases even painful (photic allodynia). Patients with visual snow syndrome can suffer continuously from photophobia and be severely distressed by it (15; 53).

Nyctalopia is defined as a difficulty seeing at night or in the dark and can be a manifestation of severe eye disorders. As with all the other symptoms in visual snow, however, it is present in patients who have normal eye exams (criterion D) and is, therefore, likely due to a central visual processing alteration. It is also possible that the difficulty seeing in the dark in visual snow could be due to an increased prominence of the static when there is less ambient light.

The described additional visual disturbances can present in several combinations within visual snow syndrome; however, floaters, afterimages, and photophobia are almost invariably present and seem to represent a hallmark of the syndrome.

With regards to clinical presentation, the onset of symptoms can be sudden in visual snow in up to one quarter of the cases (32). There have also been reports of visual snow starting out as an episodic ictal disorder and then gradually evolving into a chronic condition (42; 56). The overwhelming majority of patients with visual snow, however, report a gradual onset of symptoms, with up to 40% recalling elements of the condition for as long as they can remember.

Cases of secondary visual snow syndrome have also been reported, eg, following a stroke (09; 45), the start of a new medication (16), a dramatic change in migraine, and a concussion or an infection (30).

Prognosis and complications

A prospective longitudinal study of patients with visual snow syndrome contacted 8 years after initial assessment showed persistence of symptoms in all contacted, noting that 49% of the initial cohort were lost to follow-up (19). Visual snow symptoms themselves had not worsened, consistent with clinical experience that visual snow is likely a nondegenerative disorder. There have been no reported cases of loss of vision following onset of visual snow to date, and generally the condition seems to be stable through time, albeit in some patients with periods of worsening.

There are no clearly determined worsening factors; however, recreational drug use, alcohol intake, migraine attacks, stress, and other illnesses can accentuate symptoms for a short or long period in some patients.

Clinical vignette

A fictitious patient with visual snow is described as follows:

Male patient, aged 24, with a history of episodic migraine without aura and no other prior illnesses, suddenly starts noticing, during a period of intense stress, the presence of a visual disturbance that he describes as “TV-static”. The static is black and white, and sometimes yellow or transparent. It has never gone away since the start and is more noticeable when the lights are off. It is also visible with eyes closed.

During the following days, the patient starts noticing several other symptoms. For example, objects he has just been looking at reappear in his vision once he turns away, strong lights are often surrounded by a glare and flashes, and driving at night is now difficult because he is very bothered by the luminous trails from other car lights. These new visual symptoms are associated with emotional distress and anxiety.

The patient is seen by the local GP and ophthalmologists, who find no signs of ocular disease. Given his history of migraine, the GP suggests drug treatment with propranolol and topiramate, which do not improve his symptoms, and requests a neurologic consult.

Upon taking a medical history, we learn that the patient, a college student, drinks coffee two to three times per day, occasionally drinks alcohol in moderate quantities, and has never been exposed to recreational drugs. His neurologic examination is normal and an MRI with gadolinium shows no brain abnormalities. His episodic migraine has worsened in frequency in the last few months, from a baseline of one attack every 4 to 5 months to two to three attacks per month. His chief and most worrying symptom, however, is the visual static, which has not worsened or improved since the start and is affecting his life and studies. In particular, he is finding it increasingly difficult to read and is quite distressed by the lack of a clinical diagnosis for his condition.

After diagnosing the patient with visual snow syndrome of sudden onset, we review him after a few months. He has noticed no particular change in his visual static; however, he does report that since knowing of the condition – and particularly that no worsening of his eyesight is to be expected – he has been coping much better with the visual snow syndrome symptoms.

Biological basis

The neurobiological mechanisms of visual snow are largely unknown. Neuroimaging and neurophysiological data, however, have shed some light on certain aspects of its pathophysiology.

From a clinical perspective, considering the chief clinical symptom of a whole-field visual disturbance, this is unlikely to be caused by a disorder of the anterior visual pathway, optic radiation, or primary visual cortex, given that these structures are organized in a monocular or homonymous fashion. Further, the additional symptoms of the visual snow syndrome phenotype, such as palinopsia, seem to involve the processing of visual information in the supplementary visual cortex, downstream of the primary visual cortex. Retinal electrophysiology suggests some change in rod and cone photoreceptors may play a role (60).

The possibility of a cortical dysfunction in visual snow is supported by the reports of normal eye examinations and visual evoked potentials in patients with visual snow, as well as the results from brain imaging studies, showing hypermetabolism in the region of the lingual gyrus with [¹⁸F]-FDG PET (43). The lingual gyrus is an area pertaining to the supplementary visual cortex, and which is interestingly also involved in migrainous photophobia. This same region also showed a localized disturbance in anaerobic metabolism in patients with visual snow syndrome compared to healthy controls in a study combining functional MRI and spectroscopy (34).

Cortical hyperactivity was also demonstrated in visual snow via arterial spin-labeled MRI in a study involving 24 patients with visual snow syndrome compared to healthy controls (39). Higher cerebral blood flow was found in patients over an extensive brain network, including visual and motor areas, the cerebellum, and the posterior cingulate cortex. Interestingly, these areas were the same, both when patients were at rest and when visually stimulated, highlighting that the alteration may represent a neurophysiological signature of the condition.

A similar dysfunction of visual processing in areas of the ventral visual stream was found in a patient with visual snow syndrome through [123I]-IMP SPECT, with a distribution matching the ventral visual stream (46).

Further, patients with visual snow exhibit several subtle structural changes in areas that pertain to the visual cortex and extending beyond the visual system as well (32; 43; 31).

Functional brain connectivity studies have shown that patients with visual snow exhibit a dysfunction of the precortical and cortical visual pathways, the visual motion network, the attentional networks, and the salience network (36) as well as a hyperconnectivity between extrastriate visual areas and other temporal brain regions (02). Brain network dynamic studies similarly demonstrate changes in occipital and parietal cortex compared to controls (51).

Further, neurobehavioral studies have demonstrated that patients with visual snow syndrome present coordination changes in the saccadic control system (48; 49; 50; 18), which confirm an alteration of visual processing and may also represent a misallocation of visual attention in affected subjects. A neurobehavioral study also confirms the theory of increased cortical excitability of the visual areas and further attributes it to an increased neural response to external stimuli rather than to an abnormally elevated neural noise (07).

Electrophysiology has shown that visual snow is characterized by a processing disturbance at the level of the secondary visual areas (13) as well as altered habituation at the level of the primary visual cortex (29; 59); however, the latter was not confirmed in a subsequent study (14). Magnetoencephalographic work similarly points to cortical dysfunction (22).

The high comorbidity between visual snow and migraine, as well as tinnitus and hallucinogen perceptual persisting disorder (see Associated disorders section), allows some further insight into the biology of the condition. A dishabituation mechanism similar to what has been described for migraine (12) would explain its high presence in visual snow, even if these are two different conditions. The presence of associated visual symptoms – enhanced entoptic phenomena in particular – also potentially points to a disorder of habituation and sensory processing, which could allow the perception of stimuli that are normally ignored by the brain.

Tinnitus is not only highly comorbid with visual snow but also predicts its severity. On a theoretical basis, visual snow and tinnitus could represent two different manifestations of broadly similar pathophysiology, which is the perception of a sensory stimulus that is not present or is normally subthreshold within the brain.

Finally, hallucinogen perceptual persisting disorder is a condition codified in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) (03) and characterized by the reexperiencing of perceptual symptoms (“flashbacks”) typically of visual type that follow the cessation of the use of a hallucinogen and that had been experienced during the intoxication. Occasionally, hallucinogen perceptual persisting disorder can manifest with forms of visual static, palinopsia, and flashes (01; 20). This suggests a possible common basis between the two conditions, possibly mediated by a serotonergic mechanism (16), although it must be stressed that visual snow occurs mostly in patients who have never been exposed to recreational drugs. The finding by Receptor-Enriched Analysis of functional Connectivity by Targets (REACT) that patients with visual snow syndrome have reduced functional connectivity in 5HT-2A enriched networks, largely in occipito-temporo-parietal cortices, further points to the serotoninergic involvement in the syndrome (33).

Interestingly, research has shown that in the presence of hallucinogen perceptual persisting disorder, visual snow syndrome mostly manifests without migraine, suggesting that different pathophysiological factors play a role in the overlap between these three disorders (55).

Etiology and pathogenesis

Validation of a theoretical framework regarding visual snow pathophysiology will require corroboration from experimental research. Nonetheless, some theories have been advanced with regards to the etiology of visual snow. These include: thalamo-cortical dysrhythmia of the visual pathways (27), hyperexcitation of primary and secondary visual cortices (13; 29; 59), increased saliency of normally ignored subcortical activity, or possibly a combination of all of these mechanisms (35).

The results of neuroimaging, neurobehavioral, and neurophysiological studies indicating widespread functional and structural alterations in visual and extravisual areas, together with the typical clinical picture, suggest that visual snow syndrome may represent a complex brain network disorder (25). This would justify an impairment in the filtering of irrelevant internal and external stimuli, ultimately culminating in an ongoing perceptual disorder of vision. High-field 7T MRI demonstrates microstructural changes that are most evident in the occipital cortex and thalamus, without changes in morphometry (52).

It has been reported that patients with visual snow syndrome do not respond to calcitonin gene-related peptide (CGRP) monoclonal antibodies (17).

Remarkably, it has been reported that visual snow can transform from an episodic to a chronic state after cerebellar infarction (41).

Epidemiology

A population-based study from the UK showed the prevalence of the visual snow syndrome to be around 2% and 3.7% for the visual snow phenomenon (26). The large visual snow syndrome case series published to date shows an even balance across genders (42; 56; 37), with a higher prevalence of visual snow among young populations.

A study comparing a British and Italian population with visual snow syndrome showed no relevant differences in the clinical presentation and phenotype of the condition (57). Similarly, a case series from Israel reinforced the transcultural nature of the problem (05).

Prevention

There is no established effective prevention for visual snow, as its main causes are yet to be determined.

Differential diagnosis

Confusing conditions

The main differential diagnosis for visual snow is outlined in the clinical criteria (C and D). It is important to exclude the following conditions in cases of suspected visual snow:

Migraine aura. Atypical visual aura can occur with unusual phenotypes, prolonged duration of symptoms, and in the absence of migrainous pain (44; 04). All these cases can mimic the phenotypical presentation of visual snow and, therefore, need to be considered in the differential diagnosis. Important considerations for the clinician are to determine if there are other concomitant aura symptoms, if there is an underlying migraine biology, and if there are other properties of typical aura phenomenology, such as spreading and location in a visual hemifield.

Ophthalmic disorders. Photopsia, especially when associated with a sudden increase in floaters and when more apparent in the dark, can be the symptom of retinal or vitreal detachment (08). If accompanied by glares, shimmering around objects, visual loss, and night blindness, photopsias can also be caused by both retinal degeneration and paraneoplastic melanoma-associated retinopathy syndromes. The keys to not missing the above diagnoses are a good ophthalmologic examination, including acuity, visual fields when appropriate, and a dilated fundus examination. An electroretinogram is useful when the diagnosis remains unclear (06) (see Diagnostic workup section).

Hallucinogen perceptual persisting disorder. As explained in the Biological basis section, hallucinogen perceptual persisting disorder can present with visual static, palinopsia, and flashes. Therefore, appropriate history taking needs to include an inquiry on recent use of hallucinogenics.

Diagnostic workup

The diagnosis of visual snow is mainly clinical. However, as detailed in the Differential diagnosis section, it is important to exclude underlying neurologic or ophthalmological causes of similar symptomatic presentations. For this reason, a patient with new-onset visual snow should undergo full ophthalmology examination, including best corrected visual acuity, dilated fundus exam, visual field, and electroretinogram.

A diagnosis of migraine with aura should also be excluded.

Cases with atypical symptoms (eg, static in only one part of the visual field, intermittent static, clinical predominance of additional visual symptoms such as palinopsia) or new, sudden-onset cases warrant a brain MRI.

Finally, past use of recreational drugs or the start of a new medication in the 12 months prior to symptom onset should always be investigated.

Management

Given limited knowledge of the basic biology of visual snow, there are no established effective treatments.

No systematic clinical trials have been performed in this condition to date, and all available data on treatment come from single patients or case reports.

Most available evidence suggests that commonly used medications, such as migraine preventives, antidepressants, or pain medication, do not consistently improve or worsen visual snow. An exception was found with vitamins and benzodiazepines, which sometimes brought benefit. However, in most cases, they did not effectively change the course of visual snow syndrome (40).

There have been some positive experiences reported with lamotrigine (54), particularly in five subjects of a 58-case series involving patients with visual snow (56). However, this medication is still far from useful in most subjects (40).

Some improvement has been obtained with nonpharmacological interventions such as tinted lenses, particularly with filters in the yellow-blue color spectrum (27), showing that other avenues aside from drug treatment need to be explored in this condition.