HPPD Studies YOUR IMPUT NEEDED

[OldSchoolAr]

This was put together and compiled by the amazing team in London.

It encapulates some of what was discussed on the call and will be forwared to DR Abraham.

 

Below is a summary of the studies that Dr Abraham suggested.  For the open label drug study I think I may have a few of the drugs wrong or misspelt,

 

Please share YOUR imput as well as what YOU think would give us the BEST OUTCOMES. What are YOU most intrested in ?

 

When it comes to crowdfunding we could run a campaign starting with a small goal that could fund a not too expensive study that the forum are interested in, this might be the recovery rate study then include a stretch goal for something more expensive such as the genetic testing study.  

 

 

HPPD StudiesGeneral notes: Dr Abraham said that he has a database of patients with HPPD that hewould be happy to share for the purposes of our research. He mentioned that patients are very widely geographically dispersed, however he has quite a few European cases and most he thinks would be willing to take part in research.

 

STUDY 1: Brain imaging study using MRI of patients with HPPD and people with no HPPD

 

This would help us understand better the pathways that are being affected by HPPD giving us more insight into the condition.

 

Study 2: Pupil dilation testStudy 2:

 

Pupil dilation testDr Abraham noticed that HPPD patients seemed to have more dilated pupils than people with no HPPD.  This is a symptom of a hyper-aroused automnomic system.  A simple test measuring pupils size of patients in controlled lighting conditions verses control would test this hypothesis.

 

Study 3: PPI (pre pulse inhibition)

 

When people have a pre warning on a sound they are less likely to be startled, however in patients with schizophrenia the pre pulse does not seem to affect the startle response.  This is thought to be related to the dopinergic system, other conditions such as ADHD,  OCD and Tourettes also show reduced PPI.  Dr Abraham hypothesis that HPPD patients may have reduced PPI suggesting that the pathway causing the condition may be similar (but less pronounced) to schizophrenia.

 

Study 4: CFF and dark adaption

 

Dr Abraham said that people with HPPD have very bad night blindness

 

Study 5: Genetic vulnerability

 

Dr Abraham applied for funding for this study 3 times, he believed there are specific genetic vulnerabilities in patients with HPPD.  He is happy to share the information on the genes that he thinks are relevant.  If a genetic study is to be conducted it would be interesting to do this in conjunction with study 6 (below) to see if genes could be used as a tool to predict the duration of HPPD.

 

Study 6:Recovery rate

 

The study would investigate what proportion of people with HPPD recover.  From Dr Abrahams observations those who do recover do so within 5 years and around 50% recover.  He suggested that it may be possible to do this study using surveys and there are special validated ways of doing this to ensure the findings are robust.  This includes having face to face interviewers. Interviewing people twice by two differentt interviewers to make sure responses match and also using various other techniques.

 

Questions to include:What initiated your HPPD?

How long ago did you first experience HPPD?

Have you symptoms changed since you first experienced it?

Have you experienced any psychiatric co-morbidities?

Does the intensity of your HPPD vary and what causes variations in intensity?

Does anxiety influence symptoms?

 

Study 7: Open-label study on the effectiveness of treatments for HPPD

Select drug treatments that are thought to improve HPPD symptoms and do a cross over study using questionairees to measure the effectiveness of each treatment and any associated side effects.Treatments to test include:

 

Treatments to test include:

 

Clonidine which is an alpha 2 agonist

Festidalcholine (not sure if that is the right name) which improves the eye? It helps

with fatty acid metabolism and improves nerve cell integrity

Methylfolate – this is the active form of folate and ¼ of depressed people lack the

enzyme that converts folate to it’s active formStudy

 

8: Anxiety study

 

Many people with HPPD comment that anxiety makes it worse.  It is possible to test this theory and see if anxiety is a trigger for more intense symptoms. Anxiety can be triggered using CO2 (I think).  A study could be designed that measures this, if anxiety is a trigger than ways of reducing anxiety could potentially be used as treatment.  This includes meditation, yoga, maybe other forms of exercise depending on the individual such as martial arts and then improvements could be tested.  Dr Abraham emphasized that meditation has been shown to significantly reduce anxiety.

[Mr.50's]

I'm really liking study 7 so we can test new meds, seems like the most logical way to find a cure lol but study 6 is also interesting to know your chances with this fun disorder

[mycall81]

I believe imaging and genetic testing are crucial. I am scheduled to undergo an fMRI within the next 2 months. I wonder if it will show anything.

I wonder what the definition of recovery is. Would it be complete absence of visual disturbances or the adaptation to the visual changes?

I am also just starting a trial on Clonidine per Dr. A's recs. I am happy to chime in with any effectiveness.

My HPPD had seemingly resolved over many years. However, it recently found its way back. The return may be due to cannabis or triggered by a migraine headache.

I believe there needs to be a focus on detailed history of any comorbid conditions such as migraine as people with persistent aura have such a similar presentation.

[OldSchoolAr]

Thanks for your imput! Thats very helpful and i agree.

I will relay all responses back to the team in London.  They want to hear from us "sufferers".. what we feel would be most beneficial, so we can move in that direction quickly.

[OldSchoolAr]

Also, if aneyone has any additional ideas for studys, please suggest here. Although, it has to be "realistic" and do-able..

[Jay1]

Yes, i think scans and genetic tests are the most important, at this point.

 

We could guinea pig meds for years with basically guess work... what we need is a clear starting point to target. This will hopefully show with scans and genetics.

[OldSchoolAr]

 

what we need is a clear starting point to target. This will hopefully show with scans and genetics.

 

Awesome.. well said Jay!

[onelovez]

We have limited resources so we should focus on the most important things first. Right now I would focus on brain scans together with genetic tests.. the genetic tests seem to be even more important - they may give us great insight into what study we should do next - am I right?

I think we should hold on for a while with trial studies, until we gather more evidences.

This is completely random example - what if the genetic tests shows that none of us need supplementation of Methylfolate - the missing enzyme in depressed patients. In this case there would be no point doing a Methylfolate trial - we save up time and resources.

Also we should write down more medicines to choose from and then think about which ones we want to try.

(eg. There are some medicines that seem to be helpful in controlling tinnitus - would they help in controlling other HPPD symptoms? eg Acamprosate.

http://www.evernote.com/l/AbSdQyCG9BtFxbgUH-dPZ2vaP_wp2E0MhAI/ )

We can try some of the new drugs ourselves to see if we think they may have any potential.

 

 

 

 

The studies I support in the order of highest to lowest priority:

 

5 - Genetic vulnerability

Yes, yes, yes.

 

6 - Recovery rate

Only if it could give some insight into possible cures - then yes. I have a feeling it could.

 

1 - Brain imaging study using MRI of patients with HPPD and people with no HPPD

 

Yes. What about other tests though? like PET/SPECT? or would MRI be totally sufficient?

qEEG - i guess its not needed since there is enough study on it already right?

 

3 - Study 3: PPI

If it can give insight into cures then yes.

 

2 - Pupil dilation testStudy 2 

Shouldn't waste much of our resources - we can do it on the side together with some other study maybe.

 

7 - Open-label study on the effectiveness of treatments for HPPD

 

Festidalcholine which improves the eye - in my opinion we should focus on cognition (would you rather think clearly or see clearly ;p) - unless festidacholine can affect cognition.

Methylfolate - like I said above, lets do genetic tests first

 

Little doubts about this one:

4 - CFF and dark adaption

What if we spend time doing it and the answer will be "yes". Does that info matters a lot to us and would it be worth the time?

[Granite]

I'm interested in Study 5.  I had an exome sequencing test done that showed a defect in the FLNA gene.  The result showed uncertain significance because I'm the only one in their entire database that has it, and they suspect it could relate to: X-linked periventricular heterotopia (PVNH) or the bigger one X-linked recessive neuronal intestinal pseudoobstruction.  The latter being more interesting to me, obviously because I'm suffering with a nervous system disorder.  I also have diagnosed intestinal obstruction without evidence of a blockage.

 

In regards to HPPD, with the myriad of symptoms I have, the most pertinent would be Illusory Palipnopsia (afterimages/trails/snow/ghosting),

 

So, is this an area of interest to Dr. Abraham?

[VisualDude]

It is not clear to me where this is going.  So a few questions:

 

This appears to be a list, suggested by Dr A, of options/direction researchers can go.  The question is, who is doing what?

 

Regarding the "amazing team in London", is this their list from conversation with Dr A?  Or is this list from your conversation?

 

What role/direction is the London group pursuing?  Seems that they have already have a project defined and we are piggy-backing on that?  So how do we fit in their model?

[Jay1]

It is like this:

 

Beckley are currently conducting test on how LSD works on the brain.

Because of this, OldSchoolAr got in touch to ask them if they knew about HPPD and would consider helping us.

They replied that they would like to hear more and me and OldSchool had a conference call with their head of fund raising.

She was interested and thought that she could 1) Help raise money and 2) use that money for the Beckley group's scientists to perform whichever tests were deemed the best to persue.

She asked if we could put her in touch with a doctor with experience with HPPD studies so that she could better understand the condition and also to take a "plan of action" to the Beckley doctors.

She had a conference call with Dr Abraham and OldSchool where the above ideas were put forward.

The ideas are being put forward to the community and we can suggest which ones we think should be presented to the Beckley doctors, including any that are not on the list but could be usefull.

 

So, the HPPD funding and studies are completely separate from their previous studies. Dr A will work with and help their doctors to provide ideas and info, but their doctors will be carrying out the tests in London. They also seem keen for the forum to have input and ideas, which is why this thread was started. Dr A had some good ideas, but there is always room for more ideas that could be presented too.

[umit]

I have some information like my experience buth cant explain or dont know how to link in sciencitfical information i wis i could or help input information the only what can bring is practising sport have strong relief in some symptomps like pysg libido congetive now txn to sport i feel the most time relax

Melatonine have some postieve effect on moving objects

[OldSchoolAr]

G

[VisualDude]

Thank you for the synopsis.  As for options:

 

#1 Brain imaging.  To date no abnomalities have been seen with MRI.  Perhaps fMRI would be useful, but this method would be $$ and probably not yield much info.  'Damage'/alteration is diffuse and tiny ... even if the symptoms are awful.

 

#2 Pupil dilation.  This is apparently known.  ANS problems are known with CNS problems - particularly with dopamine 'shortage'.  This test should be performed anyway if any physical examinations are involved.  It is simple and takes just a minute or two.

 

#3 PPI.  HPPDers usually have anxiety issues ('vigilant' attention state).  As long as this isn't arduous, it is good to add to the physical exam list.  It shouldn't be costly - but I don't know what is involved.

 

#4 CFF and dark adaption.  I am not specifically familiar with CFF ... so will fly by seat of pants on this topic.  Contrast, both spot and overall light adaption, involves dopaminergic function.  Each photo-receptor is connected to a dopaminergic neuron.  We need to isolate this system and see if this/these symptoms respond to dopamine agonists, even if other symptoms do not respond positively.

 

Flicker response is known to change with acetylcholine (which would be affected by Keppra).  I don't know if this has relation to CFF.  However in reading about CFF, they speak of the relationship between cone behavior and rod behavior being affected by flicker rates.  In general, information pathways from cones primarily feed to Focal Visual Processing - which is detail based, analytical.  Information from rods primarily feed Ambient Visual Processing - which is vigilant based, fight/flight.  If these two systems do not coordinate correctly, many cognitive symptoms result - often those reported as HPPD or comorbid HPPD.

 

That all said, some good info may be attained.  Suspect CFF testing would take some time and perhaps this isn't to best place to pour resources - as we already know some of this stuff.

 

#5 Genetic vulnerability.  IMO this is vital to start collecting data.  Statistics need lots of samples, so there needs to be many participants.  Since vulnerability probably involves multiple places, even more participants are needed - but this will help find out which med a person responds to and why.  Tests should involved many SNPs - ideally all.  As of last year, complete genome tests are now less than $1000.  That is still costly but now about what a MRI costs.  I've already spoke much on this topic so will leave it at this being extremely important in order to progress with knowledge and treatment of HPPD.

 

It is very important to tie a symptom and med response survey with each sample.

 

#6 Recovery rate.  This info needs to be collected, following the progression of worsening, then getting better, stalling, regression ... or going sideways.  A comprehensive survey need to be taken and tied with genetics studies.

 

#7 ... effectiveness of treatments.  How each person responds (including each symptom) needs to be documented.  While it is ideal to diagnose then treat, there is no established protocol to do so.  And pharmacological response is valid method to study.

 

#8  Anxiety study.  It is not clear what we will learn from this.  We already know that most HPPDers suffer anxiety.  However, some have symptoms tied with levels of anxiety, yet others do not.  Dr A has already stated that treating anxiety and/or depression is the most effective treatment of HPPD.  It is also known that chronic anxiety is unhealthy for both brain and body.

 

Notes:

 

Regarding statements of the 'already-known' nature: These are already known in medicine but not necessarily 'collected' into the set of HPPD/VS information.  Since medical studies are highly specialized, knowledge is highly fragmented.

 

Good groundwork has already been established.  Building from these is important.  Question raised need answering ...

 

QEEG studies show HPPD brains in constant 'pre-seizure' state.  Med responses usually follow this as well: Klonopin (gaba), Dopamine (D2), Keppra (psudo anti-cholinergic) -- these are inhibitory, thus calming activity.

 

 

Well, this is my 2 cents.

[Jay1]

Yes, I was a little confused with the MRI idea as I was sure that didn;t show much/anything... But couldn'f remember properly.

 

Maybe Dr.A has something new regarding that that he thinks is worth testing... Did he send any notes through, OldSchool?

 

Further, controlled qEEG tests would seem a better approach?

[Ghormeh Sabzi]

If you want to see the correlation between HPPD and VSS (Visual Snow Syndrome) patients PET scans have already shown abnormalities in metabolism of glucose (this is a very important area to clear up and so would be my suggestion). 

 

DaT/SPECT scans could also be considered which measure the activity of the dopamine transporter if it is thought this could reveal any information.

 

fMRI could be used to see how a person responds to particular stimuli.

 

All these tests are more revealing than qEEGs, I think.

[OldSchoolAr]

That sounds great Visual!

I will forward your post thru to them also..

 

 

Did he send any notes through, OldSchool?

 

No.. Dr A did not send anything regarding this...yet

[umit]

I am asking very simple wat could to be the fuel of this condition ? I have the feeling that somthing is stuck in my mind somtimes when i drink alchol i am olmost symptom free for 1 day exept after image

[VisualDude]

If you want to see the correlation between HPPD and VSS (Visual Snow Syndrome) patients PET scans have already shown abnormalities in metabolism of glucose (this is a very important area to clear up and so would be my suggestion). 

 

DaT/SPECT scans could also be considered which measure the activity of the dopamine transporter if it is thought this could reveal any information.

 

fMRI could be used to see how a person responds to particular stimuli.

 

All these tests are more revealing than qEEGs, I think.

 

As a side note, functional imaging and EGGs need to be done after a person has discontinued any meds relating to HPPD for several days (weeks with Klonopin or other meds with long half-lives).  This exclusion might be burdensome for those who have stabilized with a particular medication routine.

 

Also, PET scans are more expensive than CAT or MRI scans and involve the injection of radioactive materials.  These factors should be considered from cost/benefit and patient consent standpoints.  PET scans are poor for diffuse issues.

[Ghormeh Sabzi]

As a side note, functional imaging and EGGs need to be done after a person has discontinued any meds relating to HPPD for several days (weeks with Klonopin or other meds with long half-lives).  This exclusion might be burdensome for those who have stabilized with a particular medication routine.

 

Also, PET scans are more expensive than CAT or MRI scans and involve the injection of radioactive materials.  These factors should be considered from cost/benefit and patient consent standpoints.  PET scans are poor for diffuse issues.

 

Of course people need to know the risks and agree to them, and consent issues would be appropriately sorted whatever the tests by experienced researchers/doctors.

 

R.e. cost and benefit, since PET scans were previously used by the VSS research team and because there is a clear relationship between the two disorders it makes sense to see if the results can be replicated, particularly by HPPD patients who have symptoms which are particularly symptomatic of HPPD (e.g. warping of objects). If you can show they are the same thing research can then be joined with them and you have a bigger pool of funds and resources to research with (although I think every case is different in either case). You can also see relationships between migraine and epilepsy, for example, as PET scans have been used extensively in those areas. I would imagine a room would be hired out for a certain amount of time and this reduces costs.

If I recall correctly the VSS fundraisers raised $20k for their initial study of 17 patients using PET scans, and the money was also used to help with travel/accommodation costs of patients, although I don't know if money came from elsewhere from institutions/grants or whatever to help with the costs because everything included, that seems particularly cheap.

But cost does need to be seriously considered. How much can we realistically raise? Most VSS patients would presumably prefer to donate money to the research already taking place, which limits numbers already.

A large cost which also needs to be considered is having the tests results analysed. This is particularly pertinent to gene testing, as we would need a geneticist on board not only to find associations between data, but also to draw conclusions from the data. I don't know whether the Beckley Foundation is the type of organisation which would be involved in that sort of thing. From our viewpoint I think gene testing is the most important area for loads of reasons (and as you suggest it is imperative it is linked with a survey), but I think from their standpoint it should also be considered important as they are an organisation which promotes the use of certain drugs in certain situations and so they need to be able to screen to exclude certain people from treatment studies if they are susceptible to HPPD or other drug-induced disorders.

You raise a good point r.e. medications and it is something I have considered as well. This is one of the many reasons why I think it's really important to get the comprehensive survey completed first before steaming ahead with tests etc.

[VisualDude]

It is good to show relationship between HPPD and VS and migraine and epilepsy.  Again that has (at least sort of) been seen.  The negative side is that there is no treatment for VS and poor treatment for epilepsy ... so it doesn't do much for us in the short-medium term.

 

Hopefully Beckley Foundation would be interested in finding out who the vulnerable population are since they hope to legalize recreational drugs.  It will be interesting to see how this all flows/develops.  Genes determine strengths and weaknesses.

 

Have no idea how they would analyze gene data.  A mathematician/computer programmer would be the most likely needed.  There is software out there but it doesn't seem to be oriented to pattern recognition.  Not sure what MD personnel would be needed.  And of course, almost no one works free anymore - life has gotten too expensive for volunteers who are not already well off.

 

Wonder why Dr A has not been able to get genetic-test-funding those 3 times?

[Ghormeh Sabzi]

Certainly the treatment options for epilepsy aren't perfect, and it is not universally treated, but many people are successfully treated, and it is actually one of the very few disorders that can truly be cured, rather than just treated (although only in extreme cases of removing areas of the brain that is causing the epilepsy, and removing that part of the brain shouldn't cause significant issues!) There are also innovative treatment techniques available like deep-brain stimulation.

 

But the idea of showing the relationships with VSS is so that researched could eventually be pooled. If you have a bigger group of people and more resources, you have more chance of getting stuff done, and a much greater chance of successfully applying for things like grant as you are applying for a larger community. Gene testing is key to showing relationships, and I hope something can be worked out on this front, but I just don't know how realistic it is in the short-term. Clearly a full sequence is the preferred option, but the cheap 23andMe option might be more realistic, even though it won't be as revealing. Perhaps you can make another appeal for samples? 

 

Genome-wide association studies/disease gene identification is required and a geneticist with experience of this is essential. I hope inquiries can be made to Beckley regarding gene testing but I'm not hopeful of the outcome. I've found a couple of good (although very expensive) books to learn more about this. Dr A probably wasn't able to get funding simply because it couldn't be shown there was enough people with the disorder to make it worthwhile so it wasn't considered 'important' enough.

 

Treatment trials are actually starting next month as part of the VSS research, although I understand the treatments they will be trialing aren't for long-term use, but rather to give a better indication of things which might work (much like Dr A informal study). One of them is well-known as a treatment option to this community anyway, although they are using intravenous injections.

[Mr.50's]

Study 1:brain imaging, we need to know what's happening before we can develop treatments and medication, then Study 2:effectiveness of treatments and medications

[mycall81]

What is the treatment option that the VSS community is working on? Anyone know?