infection

Alice in Wonderland Syndrome – is there a pyroluria connection?

June 25, 2021 By Trudy Scott 48 Comments

I first learned about Alice in Wonderland Syndrome (AIWS) during one of the Anxiety Summits. I’m surprised at how many queries I get about this syndrome and the fact that everyone who has reached out also has the social anxiety condition called pyroluria or suspects they have it.

This 2017 paper, Alice in Wonderland Syndrome: A real life version of Lewis Carroll’s novel, describes it as follows:

Alice in Wonderland Syndrome was originally coined by Dr. John Todd in 1955. The syndrome is named after the sensations experienced by the character Alice in Lewis Carroll’s novel Alice’s Adventures in Wonderland. Alice in Wonderland Syndrome consists of metamorphopsia (seeing something in a distorted fashion), bizarre distortions of their body image, and bizarre perceptual distortions of form, size, movement or color. Additionally, patients with Alice in Wonderland Syndrome can experience auditory hallucinations and changes in their perception of time. Currently, there is no known specific cause of Alice in Wonderland Syndrome. However, theories point to infections such as the Epstein-Barr virus, medications such as topiramate and associated migraines.

You can read about all the types of visual and non-visual distortions in this paper: Alice in Wonderland syndrome – A systematic review. This paper also includes a list of conditions in which Alice in Wonderland syndrome has been described in the literature, with infections and migraines being very common. The authors also feel that what we see in the published literature may only be the tip of the iceberg:

Since 1955, no more than 169 case descriptions of AIWS have been published. The literature indicates that this may be only the tip of the iceberg, with many individual symptoms of AIWS being experienced (albeit occasionally and only fleetingly) by up to 30% of adolescents in the general population.

The published case numbers have increased slightly (this paper was published in 2016) and it’s reported that many of the 30% of adolescents with AIWS experience non-clinical symptoms i.e. they are not severe enough to need treatment.

I still find “up to 30% of adolescents in the general population” to be very surprising for a syndrome which was once considered very rare and is frequently misdiagnosed.

Read on to hear from some folks in my community who have reached out and described their AIWS episodes. They all have pyroluria and I’d love to know if there is a possible connection.

Everything either looks really far away but massive or really close up but tiny

Sallie, a mom in my community, shared about her son and what he experienced in the comments section of the pyroluria prevalence and associated conditions blog. During his episodes, everything either looks really far away but massive or really close up but tiny:

I believe he has Alice in Wonderland syndrome. I have taken him to GP’s, pediatricians, optometrists, opthamologists and no one knew what was wrong. I spent about 6 months researching the possibilities myself and came across AIWS. When I showed him some of the journal articles, he was so relieved to finally have an answer. Since then, I have had a gut feeling that pyroluria and AIWS may be linked somehow.

She believes his AIWS may have been triggered by an infection when he was around 6 years of age. He developed sudden onset of vomiting, fever and delirium:

Still to this day, he distinctly remembers this night and recalls (like it was yesterday) not being able to stop looking at his hands because they were changing size and how far away/close up they were.

Once he was old enough to articulate what he was experiencing, he was able to tell me he feels weird, like he needs to go to a pitch-black room and lie down. Sometimes it coincides with a headache.

Everything suddenly appears as if far away then everything either looks really far away but massive or really close up but tiny. He feels dizzy while this happens also. Stress definitely increases the number of AIWS episodes.

Infections are reported as one (of possibly many) root causes of AIWS: “Reported causes include infection (especially with Epstein Barr virus), migraine, epilepsy, depression, and toxic and febrile delirium.”

Infections are common mental health triggers. Strep as a trigger for PANDAS/PANS is a classic example. I blog about Bartonella and sudden-onset adolescent schizophrenia here.

He has pyroluria and stress increases the number of episodes he experiences. My question is this: is there a link between the dumping of zinc and vitamin B6 during these times of stress and episodes of AIWS?

The feeling of being extremely small somatically (or physically), like how you feel when in a football stadium

Mike is a 21 year old male and thinks he may very well have pyroluria based on the questions. He also shares this in the blog comments about his AIWS experiences:

I have experienced sensations similar to Alice in Wonderland Syndrome throughout my life, more so during periods of stress. The feeling of being extremely small somatically (or physically), like how you feel when in a football stadium.

Again, he has pyroluria and his symptoms are worse during periods of stress. Keep in mind that stress makes pyroluria symptoms more intense too.

She usually experiences objects/people smaller than what they are but her more pronounced symptoms are sound distortions

Brenda, another mom in the community, shared this about her daughter’s dreams and PMS on the pyroluria questionnaire blog:

I’m quite certain that my 17 year old daughter has pyroluria. I counted 23 symptoms that she definitely exhibits. Her dream recall is so poor that she insists she doesn’t dream at all. I’m going to start her on zinc, B6 and evening primrose oil right away. Her PMS/premenstrual syndrome is so severe that I had decided to see a gyno to discuss birth control pills. Of course I won’t after listening to your interview with Karla Maree (on the Anxiety Summit).

She also asked if I was familiar with Alice in Wonderland Syndrome and if so do I think it may be connected to pyroluria? She shares this about her daughter’s AIWS experiences:

My daughter has experienced occasional Lilliputian (trivial or small) hallucinations since childhood. She usually experiences objects/people smaller than what they are but her more pronounced symptoms are sound distortions. She hears voices/noises (real, not imagined) much louder than they are in reality.

She does not have migraines, has never had mononucleosis or any of the other conditions listed as possible causes of Alice in Wonderland Syndrome. That’s why I’m thinking it may be caused by nutritional deficiencies.

This was my introduction to this syndrome and I appreciate her for asking the question. I did some reading of the research and the word “hallucination” got me thinking that a pyroluria connection was possible. The original work by Dr. Carl Pfeiffer with pyroluria was with individuals with schizophrenia.

However, the second paper mentioned above does state that “AIWS is characterized by perceptual distortions rather than hallucinations or illusions and therefore needs to be distinguished from schizophrenia spectrum and other psychotic disorders.”

We clearly have much to learn and I’m still curious to find out how often these two conditions do overlap – pyroluria/social anxiety and Alice in Wonderland Syndrome.

Resources if you are new to pyroluria

Pyroluria is a social anxiety condition and the physical and emotional symptoms are caused by deficiencies of vitamin B₆ and zinc. When you experience high levels of stress, vitamin B₆ and zinc will be further depleted, so you may notice worsening symptoms and more anxiety. Here is the symptoms questionnaire and additional resources if you are new to pyroluria:

Pyroluria questionnaire (from my book, The Antianxiety Food Solution):
Pyroluria prevalence and associated conditions
Social anxiety caused by pyroluria: oxytocin, the vagus nerve, pectus excavatum and Ehlers-Danlos Syndrome
My book, The Antianxiety Food Solution, has an entire chapter on pyroluria

Have you (or a family member) had episodes of Alice in Wonderland Syndrome? And do episodes coincide with times of added stress?

Do you also suspect pyroluria and has the pyroluria protocol or other nutritional interventions helped to reduce or stop the episodes?

I’d love to also hear anything else you’re willing to share: age at onset, age AIWS stopped, do you suspect an infection as the trigger (or a medication or toxins or something else?), do others in the family have AIWS episodes and how would you describe your AIWS episodes?

Feel free to post any questions here too.

Increased sociability improves vagus nerve function: the role of social anxiety, pyroluria and low zinc

December 13, 2019 By Trudy Scott 43 Comments

With the objective of taking a deeper dive into some of the favorite topics of the recent Anxiety Summit: Gut-Brain Axis, today’s blog is about the vagus nerve since Dr. Navaz Habib’s interview, Vagus Nerve Activation to Reduce Anxiety, was voted one of the favorites. I’m focusing on one tool that improves vagus nerve function that we didn’t have time to get into in great detail – and that is how increased sociability helps. It’s all good and well to recommend getting out and hanging out with more people but if you have the social anxiety condition called pyroluria it’s really challenging, hard work and very stressful. Added stress makes pyroluria worse so it becomes a vicious cycle.

Let’s start with the research that supports the connection between the vagus nerve and increased anxiety and mood problems. In the interview with Dr Navaz, we discussed this paper: Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders which states that “vagus nerve stimulation is a promising add-on treatment for treatment-refractory depression, posttraumatic stress disorder, and inflammatory bowel disease” and how stimulation of vagal fibers that go from the gut to the brain (afferent fibers) influences neurotransmitter production and “play crucial roles in major psychiatric conditions, such as mood and anxiety disorders.” The gut bacteria play a major role too, “partly by affecting the activity of the vagus nerve.”

In our interview we end with very practical ways to activate your vagus nerve

Deep breathing exercises (mentioned in the above paper, together with yoga and meditation) and cold showers (which makes you breathe harder)
Gargling and using the gag reflex
Humming, chanting and singing (I used these approaches for my vagus nerve issue after my terrifying plane ride. GABA also helped with the voice/throat spasms I experienced – more here on that)
Auricular acupuncture (which is also very effective for addictions)
And finally, social interaction or increased sociability, which I want to cover today

The research on the vagus nerve and being more social

Let’s look at the research on the vagus nerve or vagal tone and being more social. This paper, Upward spirals of the heart: autonomic flexibility, as indexed by vagal tone, reciprocally and prospectively predicts positive emotions and social connectedness, reports that that vagal tone and connectedness or being more social is a two-way street i.e. it’s reciprocal

“…increases in connectedness and positive emotions predicted increases in vagal tone” and
“Adults who possessed higher initial levels of vagal tone increased in connectedness and positive emotions more rapidly than others”

In summary, the more social and happy you are, the healthier your vagus nerve is and a healthier vagus nerve leads to feeling more connected and happy.

This study was done with adults in a community-dwelling setting over 9 weeks: “adults were asked to monitor and report their positive emotions and the degree to which they felt socially connected each day.”

Address pyroluria in those who have social anxiety

Pyroluria, the social anxiety condition, was not part of the study because it’s under-recognized as a factor in anxiety. I’d like to propose that we address pyroluria in those who have social anxiety in order to further improve social connectedness and their vagus nerve function.

Many folks with pyroluria put on a brave face in social settings and even “extrovert” which is extremely stressful. The added stress makes pyroluria worse (zinc and vitamin B6 are dumped in much higher amounts) so it becomes a vicious cycle.

Others, who are not willing to even show up because of their severe social anxiety, are not getting that social interaction and connectedness that is so crucial for improved vagus nerve function and better overall health.

Here is the pyroluria questionnaire and the pyroluria/introvert connection.

Connecting the dots further we have

research that reports that vagus nerve stimulation has potential in autism treatment and we know pyroluria and social issues are common in autism
one of the key nutrients for pyroluria, zinc, plays a role in vagus nerve function
another key nutrient in pyroluria is vitamin B6 and it plays a role in reducing inflammation
according to the vagus nerve study above, the vagus nerve “plays important roles in the relationship between the gut, the brain, and inflammation”
both zinc and vitamin B6 are needed for neurotransmitter production, so increasing both GABA and serotonin will further improve mood and reduce anxiety
and finally, the more social and happy you are, the healthier your vagus nerve is and a healthier vagus nerve leads to feeling more connected and happy

By addressing the social anxiety called pyroluria with a foundation of zinc and vitamin B6, we can increase sociability and thereby improve vagus nerve function.

UPDATE 5/7/2020:

Social isolation during the coronavirus pandemic – other vagus nerve exercises

This blog is very applicable now during the coronavirus pandemic. I’ve made an update because I feel we need to start thinking about the longer-term adverse impacts of social isolation and work on other ways to improve vagus nerve function during isolation or quarantine.

This can include any or all of the ways mentioned above: deep breathing exercises, yoga, meditation, cold showers, gargling/gag reflex, humming/chanting/singing and/or auricular acupuncture.

Do you find you have better vagus nerve function when you are more sociable? What of these vagus nerve exercises have you been doing and found helpful during isolation? Do you have any other favorite approaches like using essential oils or anything else?

Vagus nerve stimulation to treat respiratory symptoms associated with COVID-19

This paper reports benefits in 2 patients with coronavirus – Use of non-invasive vagus nerve stimulation to treat respiratory symptoms associated with COVID-19: A theoretical hypothesis and early clinical experience

Both patients reported clinically meaningful benefits from nVNS therapy [non-invasive vagus nerve stimulation].
In Case 1, the patient used nVNS to expedite symptomatic recovery at home after hospital discharge and was able to discontinue use of opioid and cough suppressant medications.
In Case 2, the patient experienced immediate and consistent relief from symptoms of chest tightness and shortness of breath, as well as an improved ability to clear his lungs.

The authors also share that “vagus nerve stimulation has been demonstrated to block production of cytokines in sepsis and other medical conditions.”

With this virus being novel and with everyone learning we are still appreciative of small case reports like this and hope to see bigger studies done. Until then there is other evidence of the overall importance of the vagus nerve in helping to regulate lung infection and immunity.

The nVNS therapy mentioned in the COVID-19 paper is an external device that delivers “a proprietary signal through the skin to either the right or the left branches of the vagus nerve in the neck.” It’s not something I’ve used personally or had clients use so please share if you’ve had success with this device or a similar device.

Loving social isolation and thriving during coronavirus

On the flip side we also need to consider that there are some individuals who are loving social isolation and thriving emotionally. I share some feedback from folks in my community:

Elissa: “As an introvert, my mental health has never been better ☺️. Loving isolation life.”
Drew: “Loving it in many ways. Dreading the hedonism starting up again…”
Tiffany: “My anxiety levels have decreased and I have decreased my anxiety meds! I think it’s because the demand to produce has decreased. I can actually move at my own speed in this world. I’m fortunate, though. My heart goes out to those people in medical fields. I really miss some things, like time with my dad, but we have made some adjustments, like driveway picnics.”
Katie: “I was praying for relief from the busyness. Definitely didn’t have this in mind and my heart hurts for those who are impacted. It has been a beautiful time of rest and restoration for my body and soul.”
Wendy: “My life is usually slow paced and introverted. Now it’s more so and I’m finding the less I do in a day, the better I sleep. I’m actually dreading getting back to “normal” with all the pressures put on us by extroverts. Yes I have sympathy for people suffering mentally by isolation, but for the first time I feel like my type of lifestyle is socially acceptable. I’m tired of life expectations being dictated by the extrovert half of the population.”

I appreciate these folks for sharing their valuable perspectives about thriving in these times. It reinforces how unique we all are.

If you’re struggling with social isolation…

How are you feeling and what are you most looking forward to doing once social isolation recommendations are relaxed?
I’m guessing you don’t have pyroluria but please share if you do?

If you are thriving in social isolation…

Would you consider yourself an introvert /a contented introvert?
Have you got pyroluria and has addressing it nutritionally in the past allowed you to be more sociable or at least less anxious when you are in crowds?
How are you feeling during social isolation and what do you love the most right now?
What are you not looking forward to once social isolation recommendations are relaxed?
And how do you plan to go back to the old “normal” or don’t you?

Please comment below and let us know where you are with social isolation during this pandemic – struggling or thriving? And what vagus nerve exercises are you using right now? Have you used an external device with success?