visual snow

Visual Snow:A Newly Recognized Neurological

Disorder

Tamara BystrakPharmD Candidate

Objectives

Introduce Visual Snow (VS) as a newly recognized neurological disorder

Highlight visual symptoms in proposed diagnostic criteria for VS

Discuss and debate possible pathophysiology behind VS

Review treatment used in recent trials and case reports

Understand the impact VS has on lifestyle

What is Visual Snow?

A disorder of altered visual perception

Patients see continuous tiny dots across the entire visual field

Analogous to the pixels on an old analogue television

Occurs 24/7 with eyes open and closed

Simulation:

Schankin CJ, 'Visual snow' - a disorder distinct from persistent migraine aura. Brain. 2014

Schankin CJ. Visual snow--persistent positive visual phenomenon distinct from migraine aura. Curr Pain Headache Rep. 2015.

http://www.visualsnow.eu/visual-snow-simulators/

http://www.visualsnow.eu/visual-snow-simulators/

Why Is Visual Snow Newly Recognized?

Visual snow was conventionally regarded as a variant of migraine aura known as Persistent Migraine Aura Without Infarction (PAWOI)

Case reports from 1995 describe patients with “unusual migraine complications” involving “persistent positive visual phenomena …usually consisted of diffuse small particles such as TV static, snow, lines of ants, dots, and rain”

Visual snow is also commonly confused with floaters by opticians and doctors

In the last few years, the medical community has begun to recognize visual snow as a distinct neurological disorder, separate from migraine

Liu GT, Schatz NJ, Galetta SL, Volpe NJ, Skobieranda F, Kosmorsky GS. Persistent positive visual phenomena in migraine. Neurology. 1995 Apr;45(4):664-8.

Liu GT, Schatz NJ, Galetta SL, Volpe NJ, Skobieranda F, Kosmorsky GS. Persistent positive visual phenomena in migraine. Neurology. 1995, 45(4):664-8. Haas DC. Prolonged migraine aura status. Ann Neurol 1982; 11: 197-199

Dr. Christoph Schankin University of California, San Francisco

Spearheading research in visual snow, with help from Dr. Peter Goadsby and the rest of the Headache Group at UCSF

Leading author of several VS studies in the last 5 years

Spread visual snow awareness by presenting at the American Academy of Neurology's 64th Annual Meeting in New Orleans and the 54th Annual Scientific Meeting of the American Headache Society (2012)

Eye on Vision Foundation. Update of visual snow study from UCSF. URL: http://www.eyeonvision.org/news/102-update-on-visual-snow-study-from-ucsf.html

Leading ResearchThe relation between migraine, typical migraine aura and visual snow. Headache. 2014

A prospective semi-structured telephone interview N=120 patients with visual snow N=70 had comorbid migraine

Positron emission tomography (PET) Scans N=17 patients with visual snow matched against n=17 control

subjects

Conclusions:•Comorbid migraine aggravates the clinical phenotype of the "visual snow" syndrome•The hypermetabolic lingual gyrus confirms a brain dysfunction in patients with "visual snow"

Leading Research 'Visual snow' - a disorder distinct from persistent migraine aura. Brain. 2014

1. A chart review of n=22 presented for diagnosis and management2. A retrospective internet survey (n = 275) of self-assessed 'visual snow'

subjects done by Eye On Vision Foundation. Two random samples from 235 complete data sets

3. A prospective semi-structured telephone interview in 142 patients (n=78 confirmed VS)

Conclusions:• Visual snow is a unique visual disturbance clinically distinct from

migraine aura that can be disabling for patients• Migraine is a common concomitant although standard migraine

treatments are often unhelpful

Common comorbidities

• 70/120 (58%) 1

• 46/78 (59%) 2

• Often present with more severe symptoms

Migraine (with or without

aura)

• Ringing or buzzing in the ears• 77/120 (64%) 1

• 48/78 (62%) 2Tinnitus

• 1/17 depression (6%) 1

• 12/53 anxiety (23%) 2

• 11/53 depression (21%) 2

• 23/53 (43%) overall 2

Anxiety and/or Depression

1) Schankin CJ. The relation between migraine, typical migraine aura and "visual snow". Headache. 20142) Schankin CJ, 'Visual snow' - a disorder distinct from persistent migraine aura. Brain. 2014

Time Course Populations

Majority young and otherwise healthy Often in the second to fourth decade of life

Trigger Most cannot remember a clear trigger A small percentage report head trauma, migraine attacks, or use of illicit or

prescription drugs precipitating initial episode of VS Aminoglycoside antibiotics, opioids

Onset At 21 + 9 years (76%) Since earliest memory (24%)

Duration visual snow rarely disappears once it appears

Schankin CJ. The relation between migraine, typical migraine aura and "visual snow". Headache. 2014

Fulton, James T., Processes in Biological Vision {online} {Corona Del Mar, CA. USA} Vision Concepts, 2000, URL:http://neuronresearch.net/vision/

Symptom Progression


Progressive Worsening

Progressive Worsening to Constant Symptoms

Stepwise Worsening to Constant Symptoms

Constant Symptoms

Entopic phenomena


ADDITIONAL SYMPTOMS

Palinopsia

Trailing: A moving object in the visual field is not perceived as one object, but as a smear of objects ’following‘ the object

Afterimages: an image continuing to appear in one's vision after the exposure to the original image has ceased


Persistence of a visual image following removal of the exciting stimulus

Photophobia

http://dxline.info/img/new_ail/photophobia_1.jpg

Sensitivity to light (too bright, painful, or both)

Nyctalopia

https://upload.wikimedia.org/wikipedia/commons/b/b6/P360_Onderdendam_goed_nachtzicht_ns_nachtblind.jpg

Impaired night vision

Entopic phenomena

Spontaneous photopsia: Short-lasting sensation of light in one or both eyes in absence of an external light sourceDescribed to patients as: bright flashes occur briefly, then fade

Self light of the eye: Patient notes luminous moving clouds of purple or orange color with eyes closedDescribed to patients as: swirls, clouds or waves with eyes closed

Visual effects whose source is within the eye itself


Entopic phenomena

Floaters: Perception of spots or strands in vision, which follow the eye movement and have the tendency to drift slowly

Blue field entopic phenomenon: Moving corpuscles (small cells) when looking at bright surfaces or the blue sky. Movement was usually pulsating (wiggling)


Proposed Diagnostic Requirements

A diagnosis of exclusion

Tegetmeyer H. [Visual Snow Syndrome: Symptoms and Ophthalmological Findings]. Klin Monbl Augenheilkd. 2016 Aug 10. [Epub ahead of print] German.

Common misdiagnoses

Persistent migraine aura

• Estimated 40% of patients with VS do not have migraines

• Symptomatic differences distinguish migraine aura from visual snow

• Episodic vs constant (or progressive)

Hallucinogen Persisting Perception

Disorder (HPPD)• Also experience

starbursts, afterimages, palinopsia

• Less than 5% of patients with confirmed VS report any drug use

• Even fewer report use of hallucinogenic drugs

• Presence in children

Psychogenic Disorder/Malingering

• Complaints often ignored or thought of as an exaggeration

• Brain scans show anomaly in lingual gyrus

• Consistency of symptomatic reports



Hypothesized Pathophysiology

Chemical imbalance of glutamic acid and gamma amino butyric acid (GABA) associated with the higher visual centers of the thalamus (upper brainstem), parietal lobe, or prefrontal lobe 1

Alterations in synaptic connectivity along the visual pathway2

Corticocortical interconnectivity Corticosubcortical interconnectivity (thalamocortical)

Hypermetabolism in the supplementary visual cortex, or lingual gyrus3

Modulates visual processing Pathophysiologic overlap with migraine but hypermetabolism not seen in interictal

migrainers without VS

3) Schankin CJ, Curr Pain Headache Rep. 2015

1) Fulton, James T., Processes in Biological Vision {online} {Corona Del Mar, CA. USA} Vision Concepts, 2000. URL:http://neuronresearch.net/vision/

2) Lauschke JL, Plant GT, Fraser CL. Visual snow: A thalamocortical dysrhythmia of the visual pathway? J Clin Neurosci. 2016 Jun;28:123-7.

When comparing the brain metabolism of patients with “visual snow” to healthy controls in [18F]-FDG PET using a paired t-test in SPM8, the right lingual gyrus and the anterior lobe of the left cerebellum were metabolically more active in patients with “visual snow.” P ≤ .001.


Visual Snow

Healthy Control


Using [18F]-FDG positron emission tomography, brain hypermetabolism in the lingual gyrus was demonstrated in B) visual snow patients. Comparison with H215O positron emission tomography after light stimulation during migraine attacks C) was used as a model for photophobia in migraineurs. This revealed the same area in the lingual gyrus being hyperperfused, suggesting some relevance of this area for visual snow pathophysiology and for the clinical overlap of migraine/aura with visual snow

https://static-content.springer.com/image/art:10.1007/s11916-015-0497-9/MediaObjects/11916_2015_497_Fig1_HTML.gif

The Lingual Gyrus

It has been hypothesized that the lingual gyrus is involved in1… Encoding visual memory Processing letters Perception of color Identification of facial expressions of emotions

Disease states involving the lingual gyrus MDD responsiveness to antidepressant treatment 2

PTSD severity 3

Social Anxiety 4

Grapheme-color Synesthesia 5

2. Jung J, Kang J, Won E, Nam K, Lee MS, Tae WS, Ham BJ. Impact of lingual gyrus volume on antidepressant response and neurocognitive functions in Major Depressive Disorder: a voxel-based morphometry study. J Affect Disord. 2014 Dec;169:179-87.3. Wang T, Liu J, Zhang J, Zhan W, Li L, Wu M, Huang H, Zhu H, Kemp GJ, Gong Q. Altered resting-state functional activity in posttraumatic stress disorder: A quantitative meta-analysis. Sci Rep. 2016 Jun 2;6:271314. Waugh CE, Hamilton JP, Chen MC, Joormann J, Gotlib IH. Neural temporal dynamics of stress in comorbid major depressive disorder and social anxiety disorder. Biol Mood Anxiety Disord. 2012 Jun 22;2:11.

1. Schankin CJ. The relation between migraine, typical migraine aura and "visual snow". Headache. 2014

5. Jäncke L, Beeli G, Eulig C, Hänggi J. The neuroanatomy of grapheme-color synesthesia. Eur J Neurosci. 2009 Mar;29

The lingual gyrus is part of Brodmann area19 (BA 19). This is in the occipital lobe of the cortex.

Schankin CJ, Goadsby PJ. Visual snow--persistent positive visual phenomenon distinct from migraine aura. Curr Pain Headache Rep. 2015 Jun;19(6):23.

Pharmacotherapy Trialed SSRIs Lamotrigine Benzodiazepines Acetazolamide Valproic acid Levetiracetam Tricyclic antidepressants Calcium channel blockers Beta blockers Analgesics Melatonin Vitamins: B6, B12, Mg Gabapentin Furosemide

Schankin CJ,. The relation between migraine, typical migraine aura and "visual snow". Headache. 2014.

Bessero AC, Plant GT. Should 'visual snow' and persistence of after-images be recognised as a new visual syndrome? J Neurol Neurosurg Psychiatry. 2014.

Table 3 Summary. Current and Past Treatment Trials for “Visual Snow” in 17 VS Patients Who Took Part in the [18F]-FDG PET Study

**11/17 patients had no current or trialed medications for VS

Patient Drugs Trial EffectPatient 2 Sertraline

Fluoxetine6 months No effect

Patient 4 BupropionTopiramate

Current No effect

Patient 5 Fluoxetine, VerapamilLamotrigine

N/A No effect

Patient 5 Sertraline N/A WorseningPatient 6 Amitriptyline,

Propranolol2 months No effect

Patient 7 Naproxen N/A ImprovementPatient 8 Sertraline

ClonazepamN/A No effect

Schankin CJ,. The relation between migraine, typical migraine aura and "visual snow". Headache. 2014

Lamotrigine Case A case report of 25 y.o female with migraine with

aura x 10yr and VS x 1yr Comorbid anxiety treated with fluoxetine 40mg daily

x 2 months No illicit drug use Normal EEG Sx: continuous bright and colorful lights, palinopsia,

floaters, nyclatopsia, photopsia Chose lamotrigine based on 2 previous case reports of

success with lamotrigine for persistent migranous visual phenomena

Unal-Cevik I, Yildiz FG. Visual Snow in Migraine With Aura: Further Characterization by Brain Imaging, Electrophysiology, and Treatment--Case Report. Headache. 2015 Nov-Dec;55(10):1436-41.

Lamotrigine Case Lamotrigine titrated up to 50mg BID After tx repetitive pattern reversal visual evoked

potentials (rVEP) show improved cortical excitability After tx patient reports

Palinopsia improved 80% Brightness/density of floaters, dots, photopsia improved 50% Improvements in blue field entopic phenomena and

nyctalopia < 30% Now able to sleep Migraine frequency from 2-3 attacks/wk to 2 attacks/month

Unal-Cevik I, Yildiz FG. Visual Snow in Migraine With Aura: Further Characterization by Brain Imaging, Electrophysiology, and Treatment--Case Report. Headache. 2015 Nov-Dec;55(10):1436-41.

Two studies presented at the European Headache and Migraine Trust International Congress (EHMTIC) in September, 2016

The Newest Data

TREATMENT EFFECT IN VISUAL SNOWPuledda F, Schankin C, Goadsby PJ

Visual Snow: a case series of 54 adults Dr. Mark Weatherall (LONDON, UK)

NOT HELPFUL

• Topiramate, sodium valproate, propranolol, amitriptyline, lamotrigine, gabapentin, nortriptyline, tizanidine, verapamil, imipramine

HELPFUL

• Riboflavin 400mg, magnesium citrate 600mg + coenzyme Q-10 350 mg, acetazolamide, levetiracetam 1000 mg

Patient Reported Exacerbating Factors

Fatigue Excessive stress Poor Diet Obsessing over sx

Drinking alcohol Smoking cigarettes Marijuana Adderall

General Treatment Points

Treatment is often aimed at comorbid depression, anxiety, tinnitus, migraine

Most drugs trialed don’t work at all Some drugs have partial effect Some drugs work but only temporarily Highest evidence for efficacy is with

benzodiazepines, antiepileptic drugs, and vitamins

Non-pharmacologic Treatment

Psychotherapy:

Diet: low salt, sugar, alcohol

Exercise

Relaxation: (meditation yoga)

Distraction

Yellow-blue color filters

Lauschke JL, Plant GT, Fraser CL. Visual snow: A thalamocortical dysrhythmia of the visual pathway? J Clin Neurosci. 2016 Jun;28:123-7.

Dr. Deborah Friedman, MDUniversity of Texas Southwestern Medical Center in Dallas

Thinks that this phenomenon is actually extremely common, just neglected in the scientific literature

Those with the disturbance "tend to be people who are very observant ... people who are really hyper-observant of their world. There's a real controversy as to how much of this is a heightened awareness of normal phenomena"

She suggests that visual snow is probably nothing more than an exaggerated type of normal visual function.

"When we have entopic firing from our retina ... if you look at the white wall and really focus on it with the right lighting, you can see it. It's the same thing with afterimages. It's normal to see afterimages…most of us pay no attention to it…but if you're a really observant person, you start noticing it, and then you notice it all the time."

MEDPAGE TODAY. Meeting coverage: Visual snow called ‘real’ not drug related. URL: http://www.medpagetoday.com/MeetingCoverage/AAN/32416

Lifestyle Impact

Difficulty readingInsomnia Chronic distraction/discomfortDietary limitationsSocial limitations: movie theater, beach, etcConstant fear of losing eyesightTreatment side effects: anticonvulsants especiallyDependent on: sunglasses, earplugs, sound machines, nightlights

SUMMARYVisual snow is a complex neurological disorder with limited data

Patients often report a sudden onset of constant symptoms, including palinopsia, entopic phenomena, photophobia, and nyctalopia

Visual snow may occur because of alterations in neurotransmitter release or synaptic connectivity along the visual pathway

PET brain scans show increased activity in the lingual gyrus

Treatment has been mostly unsuccessful, with contradictory outcomes in the literature

Increased awareness is needed to uncover more about this unique disorder

Questions

Resources Schankin CJ, Goadsby PJ. Visual snow--persistent positive visual phenomenon distinct from

migraine aura. Curr Pain Headache Rep. 2015 Jun;19(6):23. Schankin CJ, Maniyar FH, Digre KB, Goadsby PJ. 'Visual snow' - a disorder distinct from

persistent migraine aura. Brain. 2014 May;137(Pt 5):1419-28. Haas DC. Prolonged migraine aura status. Ann Neurol 1982; 11: 197-199 Liu GT, Schatz NJ, Galetta SL, Volpe NJ, Skobieranda F, Kosmorsky GS. Persistent

positive visual phenomena in migraine. Neurology. 1995, 45(4):664-8 Schankin CJ, Maniyar FH, Sprenger T, Chou DE, Eller M, Goadsby PJ. The relation between

migraine, typical migraine aura and "visual snow". Headache. 2014 Jun;54(6):957-66. Fulton, James T., Processes in Biological Vision {online} {Corona Del Mar, CA. USA} Vision

Concepts, 2000, URL:http://neuronresearch.net/vision/ Tegetmeyer H. [Visual Snow Syndrome: Symptoms and Ophthalmological Findings]. Klin Monbl

Augenheilkd. 2016 Aug 10. [Epub ahead of print] German. Lauschke JL, Plant GT, Fraser CL. Visual snow: A thalamocortical dysrhythmia of the

visual pathway? J Clin Neurosci. 2016 Jun;28:123-7. Bessero AC, Plant GT. Should 'visual snow' and persistence of after-images be recognised as a

new visual syndrome? J Neurol Neurosurg Psychiatry. 2014. Sep;85(9):1057-8. Unal-Cevik I, Yildiz FG. Visual Snow in Migraine With Aura: Further Characterization by Brain

Imaging, Electrophysiology, and Treatment--Case Report. Headache. 2015 Nov-Dec;55(10):1436-41.

MEDPAGE TODAY. Meeting coverage: Visual snow called ‘real’ not drug related. URL: http://www.medpagetoday.com/MeetingCoverage/AAN/32416

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