S2 E12: The Neuropathology of PANDAS/PANS: Dr. Brent Harris Talks about the POND Brain Bank

This podcast episode features an interview with Dr. Brent Harris, the Director of Neuropathology at Georgetown University where he wears many hats, including overseeing the Georgetown Brain Bank. In 2020, he accepted the brain of Alex Manfull who had died from complications due to PANDAS and, eventually, with the help of The Alex Manfull Fund, established the POND Brain Bank for brains and brain tissue from individuals who had been diagnosed with "PANDAS/PANS and Other Neuroimmune Disorders."  Dr. Harris talks about neuropathology, the role of brain banks in facilitating research on brain disorders, and findings from the first published clinicopathologic case report of a young adult diagnosed with PANDAS. He explains how gliosis, a marker of brain injury found in that case, can occur after a neurological insult and how it might be reversible in some cases; it is not a condition expected to be observed in healthy 26-year-old individuals.  Additionally, he emphasizes the importance of more research and better recognition of conditions like PANDAS/PANS in the medical community to improve diagnosis and treatment. The episode touches on the evolving understanding of these diseases and the critical role of clinical research and education.

The POND Brain Bank at Georgetown University

https://neurology.georgetown.edu/patientcare/pond-brain-bank/

Clinicopathologic Characteristics of PANDAS in a Young Adult: A Case Report

https://karger.com/dne/article/45/6/335/862829/Clinicopathologic-Characteristics-of-PANDAS-in-a

Disclaimer: The views and opinions expressed in this program are those of the speakers and do not necessarily reflect the views or positions of any entities they represent.

Credits: Music by Kingsley Durant from his "Convertible" album

To learn more about PANDAS and PANS and The Alex Manfull Fund, visit our website: TheAlexManfullFund.org

Follow us on:
Facebook
Instagram
LinkedIn

Episode Transcript

Speaker 1 (00:07):
Untangling Pandas and Pans is a podcast about two
little-known medical disorderscharacterized by the sudden and
dramatic onset of symptoms suchas obsessions and compulsions,
vocal or motor tics andrestricted eating behaviors, and
a whole host of other symptomsfollowing a strep or other
bacterial or viral infection.

(00:29):
I have the privilege ofinterviewing some of the top
researchers and clinicians inthis rapidly growing area, known
by various names such asimmune-mediated neuropsychiatric
disorders, infection-associatedneuroimmune disorders and
autoimmune encephalitis, orsimply PANDAS and PANS.
My name is Dr Susan Manful.

(00:50):
I am a social psychologist, theexecutive director of the Alex
Manful Fund and the mother ofAlex Manful, who died at 26
years old due to PANDAS, adisorder my husband and I knew
next to nothing about, certainlynot that our daughter could die
from it.

Speaker 2 (01:18):
This is episode 12 of Untangling Pandas in Pans,
recorded March 4th 2025.

Speaker 1 (01:27):
Dr Brent Harris is a tenured academic physician,
scientist specifically aneuropathologist at Georgetown
University.
His three main interests areneurological disease research,
medical education andneuropathology clinical service.
He is particularly interestedin understanding how mechanisms

(01:51):
of neuroinflammation and glialneuronal communication are
related to the underlyingpathophysiology of neurological
diseases such as ALS and nowinfection-associated neuroimmune
disorders like PANDAS and PANS.
My husband and I met Brent inearly 2020, in late February,

(02:18):
just before COVID emerged in theUnited States and the pandemic
would shut down the world.
The United States and thepandemic would shut down the
world.
The purpose of our meeting wasto discuss moving Alex's brain
from the brain bank at NIMH,called the Human Brain
Collection Core, to GeorgetownUniversity Brain Bank.
The meeting was facilitated byDr James Giordano, a

(02:42):
neuroethicist who, among manyroles he plays, is a professor
in the neurology andbiochemistry departments at
Georgetown.
He had met Alex in Californiajust before she died.
My husband and I made hisacquaintance shortly after Alex
died died.

(03:10):
This meeting turned out to bepivotal, a real watershed
meeting that, had it notoccurred and had Dr Harris not
had the foresight to acceptAlex's brain representing a
little-known neuropsychiatricdisorder, we would not have the
Pond Brain Bank, a repository ofbrains and brain tissue from
individuals diagnosed withPANDAS and PANS and other
neuroimmune disorders.

(03:33):
From the Pond Brain Bank.
Researchers can request samplesfor study, and medical students
, residents and fellows canlearn about these disorders,
pandas and PANS.
So much more knowledge can beunlocked from these precious
tissues at Georgetown under thetutelage of Dr Brent Harris.

(03:57):
So let's learn more about DrHarris and the Pond Brain Bank.
Dr Harris, let's get started,and actually let's get started
with the question of what wouldyou like me to call you during
this interview.

Speaker 3 (04:14):
You're welcome to call me Brent.
I'm a first name type personand I answered about Dr Harris
and Brent, but my preference isusually Brent.

Speaker 1 (04:21):
Okay, brent, good, all right.
Well, I'm going to start offwith some really basic stuff.
What is neuropathology?

Speaker 3 (04:32):
Neuropathology.
So I kind of went to medicalschool being very interested in
neuroscience and as I wentthrough I had done an MD-PhD
during my training.
So I wanted to get trained asboth a scientist and a clinician
, always fascinated about thebrain and we can talk a little
bit about that.

(04:53):
But I decided in my very lastyear of a seven-year MD-PhD
program to do neuropathology.
Pathology and neuropathologistsare the physicians who study
the brain under the microscopeat the molecular level and run

(05:18):
the laboratories that make thediagnoses that are so important.
So pathology are bad thingsthat happen to the body and
diseases, neuro being the brainand the central nervous system
and the peripheral nervoussystem, and so we're the doctors
who help to make the diagnosesof peripheral and central
nervous system disorders alldifferent kinds of things.

Speaker 1 (05:35):
So it's not always looking at postmortem tissue,
correct?

Speaker 3 (05:42):
That is correct.
Yeah, correct, that is correct.
Yeah, neuropathologists have avery it's a very narrow field,
but it is a field that actuallyhas a wide variety of things
that we do in a given day, andso neuropathologists and there
are not a lot of us out here,it's a fairly small specialty,
maybe three or 400 in the UnitedStates.

(06:04):
At most, every medical schoolhas one or two or three
neuropathologists and there area few more that are not
associated with medical schools.
But in a given day, mostneuropathologists are working
with surgeons.
They may be working with otherdoctors in the hospital if there
is an autopsy.
They're often doing teaching ofmedical students and residents

(06:27):
and fellows, and then they oftenhave laboratories that are
doing research into neurologicdisease.

Speaker 1 (06:34):
I tend to associate the neuropathology with
post-mortem brain tissue, but asyou were talking I realized
that that's not at all the case.
Certainly sounds like a fieldthat will be growing in the
future.
What do you think?

Speaker 3 (06:51):
That's an interesting question, you know.
I think it's been fairly stablein the last 50 years or so.
We certainly have more and morepeople with neurologic diseases
emerging as our populations arebecoming older and there always
will be a need forunderstanding these diseases at

(07:13):
the neuropathological level.
But whether or not it will bean increasing or decreasing
subspecialty is kind of hard tosay.
Increasing subspecialty is kindof hard to say.
In many ways neuropathology iscertainly not a moneymaker for
medical institutions because wedon't have lots of biopsies.

(07:34):
So other areas of pathologycertainly help institutions and
have different types of work,and I think that's why
neuropathologists do a varietyof different things, because we
don't have lots of brainbiopsies that we're working on
at any given time.
We don't have lots of autopsies.
The autopsy rate is decreasingin this country, but the need

(07:55):
for brain banks, which I knowwe'll talk about today, is
certainly increasing and there'splenty of work to do for
neuropathologists.

Speaker 1 (08:03):
For those that find it an interesting field, I know
that you said that you decidedto go into neuropathology in
your last year of medical school.
Were there any particularreasons that you went into that
when you were younger, forexample?

Speaker 3 (08:21):
Yeah, yeah, I was always interested in science.
As a kid, I had a dad who hasbeen, and still is, at the NIH
and is a cancer researcher there.
So I remember as a kid goingwith him to his laboratory, and
one of my early remembrances wasmuch easier to get on the
campus of NIH than it is now,unfortunately, but I remember

(08:42):
running around the fields andthen going in with him, and he
took me to an electronmicroscope, which is this big
giant microscope, a lot of tubescoming into it, and it gives
off this weird sort of sciencefiction greenish light.
And he said come here, look atthis.
And I came over, and it is amicroscope that allows you to

(09:05):
see, at a very, very highresolution, cell organelles, and
he pointed out mitochondria,and he pointed out endoplasmic
reticulum and all these coolstructures, and I loved it.
I loved it.
I went to college, though, and Iwas dead set against not going
into science, because I didn'twant to do the same thing my dad
did.
You know, we often want to dosomething different.

(09:26):
After my freshman year, I camehome, and I actually did a
rotation at the NIH, not in mydad's lab, but in another cancer
lab, fell in love with it andkind of changed my major
sophomore year to biology andvery much enjoyed my science
undergraduate career.
And then, when I was findingtime to decide what area I

(09:49):
wanted to go into after college,I really wasn't sure if I
wanted to be a scientist or aclinician.
And so I spent a couple ofyears doing a master's degree in
biochemistry to kind of fleshout that interest and decided I
really wanted to be trained inboth.
I wanted to be a clinician, Iwanted to be able to take care

(10:09):
of patients, I wanted tounderstand human disease.
But I also really wanted tofocus as a PhD scientist on a
particular area.
And I decided the neuroscienceswere very different than cancer
.
This was in the 80s and Ithought a little bit about
infectious disease because wehad just discovered HIV and AIDS

(10:33):
and I said, oh, that would be asuper fascinating area.
So that combination ofimmunology and infectious
disease almost caught myinterest.
And then I said, oh, they'llhave AIDS, you know, cured in
the next 10 years.
I'm going to go into somethingthat there's so many things we
don't know about still that Ican study for 50 or 60 years.

(10:54):
And the neurosciences, you know, caught my interest the most.
So in medical school I did thestandard MD-PhD where you start
your first couple of years ofmed school you learn about all
different kinds of diseases andhow to diagnose things and how
to treat things.
But then I started my PhD andit was molecular neuroscience
and studying GABA receptors andglutamate receptors, which are

(11:17):
the two most common kinds ofreceptors we have in our neurons
in the brain, and from that Iknew I was going to do a
neuroscience-related clinicalcareer.
I did some rotations after thatin neurosurgery, loved
neurosurgery, the things thatneurosurgeons can do amazing.
I actually was kind ofinterested in psychiatry for a

(11:39):
little while because of theoverlap of glutamate and GABA
receptors and my PhD was inpharmacology neuropharmacology.
So I thought a lot aboutpsychiatry.
But back at that point this wasin the 90s now still was a kind
of trial and error and not asmuch known about the molecular
biology of psychiatry.

(11:59):
I think if I was thinking aboutit again I might have made that
decision differently.
If I was thinking about itagain, I might have made that
decision differently.
And then I kind of settled onneurology, which was really the
treatment of disease, neurologicdisease.
Again, we didn't have a hugenumber of treatments back then.
But in my last year and I lovedall of those areas my wife said

(12:22):
you're not doing neurosurgery,you've been a student for too
long.
I had two little kids at thetime and she was right that
neurosurgery was not the bestmatch.
But I did a rotation inneuropathology, thinking that it
would be helpful for myneurology residency which I was
kind of planning on, and I lovedit.
And neuropathology is at theinterface of science and

(12:45):
medicine and so I enjoyedlearning about the nuts and
bolts of how to doneuropathology and how we serve
as consultants for theneurosurgeons and the
neurologists and other doctorsin the hospital and went full
force to pursue that combinedkind of degree.
So in the past it used to beneurologists would become

(13:06):
specialized in neuropathology,but then nowadays mostly it's
pathologists that do generalpathology and then do a
fellowship in neuropathology andthat's the direction that I
went.
I guess my earliest that I kindof knew and got interested in
the brain was in the 70s.
I loved movies in the 70s andmy favorite, favorite favorite

(13:29):
actors and directors were theMel Brooks movies and my
favorite of those was YoungFrankenstein, which to a teenage
guy had a little bit ofbodiness to it and had these
amazingly funny episodes ofunderstanding the brain and how

(13:53):
you could transfer a brain intoyou know a potential other body
and then with electricity get itto work in the Frankenstein
monster.
So Mary Shelley's Frankensteinbook I read, but then you know I
love the.
Then I love the Mel Brooksmovie Young Frankenstein.

Speaker 1 (14:11):
I wonder how many other students found their
interest in neuropathology orneuroscience watching that movie
.
So we know your interest inYoung Frankenstein and cases
like Phineas Gage and the corpuscallosum splitting.
Can you tell us how you endedup at Georgetown as the director

(14:33):
of the Brain Bank?

Speaker 3 (14:36):
Yeah, sure.
Well, I did my MD-PhD trainingat Georgetown, so I knew about
Georgetown as a student, butthere were no neuropathology
training programs in WashingtonDC back then and so when I was
applying for programs I wasworking with my wife, who really
wanted to go to business schooland she looked at a number of

(14:58):
different business schools andshe had been very patient while
I was an MD-PhD student.
So I said all right, you cankind of pick the next place we
go, as long as they have areally good, strong
neuropathology training program.
So she got into a number ofprograms she's a very smart
cookie and we made the decisiontogether as a young family to go
out to California and I startedmy residency at Stanford and

(15:21):
she started business school outthere and I had great training
and very fond memories of beingout there and learning about
these diseases in a verydifferent way than I learned in
medical school.
And from there I actually wasup in your neck of the woods and
was a faculty member atDartmouth for about eight years.
I had an excellent time being ajunior pathologist and kind of

(15:46):
learning the rules and nuts andbolts of doing neuropathology.
It was great proximity toBoston, so I had good colleagues
down in Boston that I couldshow things to and interact with
.
But once my kids kind of wentoff to college, my wife and I
started thinking about amid-career move and Georgetown
was in need of aneuropathologist.

(16:07):
And the dean of the schoolthere contacted me and said you
know, brent, would you like tocome down and give a talk?
And I said, sure, I'm happy togive a talk.
I was doing ALS research at thetime and came down and spoke
and they indicated that theyreally wanted to start a brain
bank here.
This was in 2009, 2010.
And would I be interested inlooking at a position here to be

(16:32):
the director of neuropathologyand to build the neuropathology
department and start a brainbank?
And I said that sounded like agreat idea.
It was very hard leavingbeautiful New Hampshire and
Vermont we lived in Vermont, Iworked in New Hampshire but it
was a good timing for both of usand having family down here

(16:54):
that was aging.
It was nice would come back andbe here again.
We often, you know, go off inacademic medicine to different
places based on where there arejobs and you know you don't
always go back to where youtrain.

(17:15):
So it was a nice reunion tocome back.
The neurosciences had continuedto get stronger here, and the
proximity to NIH made Washingtona really wonderful place to
kind of continue my career.

Speaker 1 (17:28):
Can you tell us a little bit about how one starts
to create a brain bank?

Speaker 3 (17:33):
Yeah.
So brain banks are kind of likethe banks that we all use, that
you put things in and you takethings out and they keep those
things stored and safe in thatbank.
Brain banks are a wonderfulinvention that's been around for

(17:54):
a while.
Some are very specific tocertain diseases and some are
more general, but the idea isthat families and individuals
who want to make a donation toscience can donate either their
whole bodies or they can donateindividual organs, like the

(18:14):
brain when they die, and thosetissues then can be examined by
a neuropathologist to look forthe specific diagnoses, by a
neuropathologist to look for thespecific diagnoses.
If it's at a medical school,the neuropathologist can use the
material to teach junior peoplewho are learning about these
diseases, and the tissues can beretained in a number of

(18:38):
different ways so that they areusable by a wide variety of
scientific investigators aroundthe world actually, who have
important questions that theywant to ask.
So when I agreed to start theBrain Bank at Georgetown, I
needed to have a little bit ofcapital.

(18:58):
I wanted to have a buy-in fromboth the university, which is
more of the research andeducation side, as well as the
hospital, which is more of theclinical side, that would
support a brain bank and that itwould serve really three
constituencies, or fourconstituencies depending on how
you look at it.

(19:19):
It would serve families whoreally could benefit from having
a careful neuropathologicalevaluation of their loved one's
brain so that they had an ideaof what the diagnosis was.
There are still diagnoses thatwhat we call the gold standard
is the autopsy, where you canhave a pretty good clinical idea

(19:40):
of what the disease is, butuntil you actually look at it
under the microscope and apathologist weighs in on the
diagnosis, you don't know.
And so for the clinicians whotook care of somebody with
neurologic disease and for thefamily who also took care of and
loved that person with aneurologic disease, this
provided a diagnostic report andthat was really important to me

(20:04):
.
It was really important thatpeople learned from this process
, so not just me working withthe brain and making my
diagnosis, but that graduatestudents who were studying
becoming PhD neuroscientistslearn about neurologic disease
for humans so that they couldcorrelate that with animal

(20:24):
studies and cell culture andcomputer modeling for neurologic
disease.
I really wanted them to learnabout the disease in humans, and
one of the courses that I teachto grad students is called the
neurobiology of disease In thevery first session.
These are for our new PhDstudents in neuroscience I take
them down to the autopsy suiteand we look at brains human

(20:47):
brains.
I also enjoy teaching youngerpeople and so every summer we
have neuroscience camps where 80or 90 high school students come
from around the country,sometimes around the world, and
they spend a week or two atGeorgetown and they learn about
all different kinds ofneurologic disease.
So we do a session with them onbrain banking and we take them

(21:10):
into the same laboratory thatthe medical students go into to
see actual human brains and tohave fix them, so they're not
infectious in any way and theylearn about it.
I teach undergraduate studentsat the university here and then

(21:34):
I have residents in pathologyand neurology and neurosurgery
who come to the brainexamination laboratory with me
and learn about these diseases.
So education is super important.
And then on the research side ofthings, with the brain bank,
we're tasked to be the stewardsof this precious material and we

(21:59):
take that responsibility veryseriously in that we are given
this very precious gift of whatI think is the most amazing
organ that we have and we needto maintain it so that it could
be usable potentially by thefamily if they needed to do

(22:19):
genetic studies in the future.
And so we freeze material downand we can make DNA and do
genetic studies if the familywishes that in the future.
But then we de-identify thematerial and we either freeze it
or we prepare it so that we canmake slides to provide to

(22:40):
people who want to research aspecific question that can only
be answered, really, withmaterial from somebody who has
passed away.
We're a little bit different inthe brain bank and in
especially neurodegenerative andneuropsychiatric brain tissue,
Very different than cancer.

(23:01):
So in cancer people are havingsurgery and the tissue comes out
during surgery and it's alsobanked.
So we have biobanks and I runthe biobank for the cancer
center of all different kinds ofcancers and we retain those as
well.
We make our diagnosis and thenwe retain tissue if the family's
allowed us to.
The family or the person inthat case, if they're living has

(23:24):
to consent to allow some of thetissue to be biobanked, and
sometimes it's biobankedtogether with blood, and so
combining the clinical diagnosis, blood and tissue can all be
very helpful.
But for neurodegenerativediseases we don't biopsy those
tissues while people are living.
There are ways of making adiagnosis and getting important

(23:45):
information about neurologicdisease through imaging studies
MRI, CT, PET scanning or fromthe fluids that bathe the brain,
called CSF cerebrospinal fluid,or from blood.
That can help make a diagnosisand that can be very important
to have in conjunction withautopsy material.

(24:06):
But the autopsy and sometimesthe end stage of disease, where
somebody has lived with adiagnosis for a long time an
amazing amount about aparticular disease by studying
it under the microscope andmolecularly that we wouldn't be

(24:31):
able to in any other way.
And so we have these tissues.
They're well curated.
So we kind of see ourselvesalso, you know, as brain bankers
, bankers, but also sometimes asbrain bankers, bankers, but

(24:53):
also sometimes as custodians ina museum, librarians, in the
library where we have thesematerials, and then somebody can
ask a very specific question.
We can go to our bank and wecan provide them then with data,
de-identified data than withdata, de-identified data and
tissue for their study.
That's kind of a long answer toa question, but I think people

(25:18):
haven't ever really thoughtabout what brain banks are.
That, in a nutshell, is what Ithink brain banks serve for the
public.

Speaker 1 (25:23):
Well, in the years that I've known you, and
certainly including thisconversation, I've come to find
your work so interesting andvaluable.
You sort of alluded to thisjust a few moments ago, but I
wonder if you could sum up whyit's so important to have
postmortem tissue.

(25:43):
Why are we studying post-mortemtissue?
What can you learn from thatthat you can't learn in other
ways?

Speaker 3 (25:53):
Sure, that's a great question.
So from every individual we canlearn something, whether
they're living or they're dead.
And by looking at the brain andthe spinal cord sometimes, and
other organs, we are able todelve into the tissue in a more

(26:19):
precise way than if we're doingimaging studies or looking at
biofluids.
And, as I said before, we don'treally biopsy the brain for
many things other than cancer.
So understandingneuroinflammation in the brain,

(26:41):
understanding neurodegeneration,is really left to when somebody
dies and has one of theseconditions or diseases, and in
those situations we can spendlots and lots of time, and the
brain is quite a large, complexstructure, as we all know.

(27:02):
But being able to look atdifferent areas that would not
be accessible during life allowsus to look at the relationship
of the cells in the tissue witheach other.
And they could be immune cellsthat are coming in from the
periphery to the brain thatwould not necessarily be picked

(27:22):
up on imaging studies.
They could be infectiousdisease that could be queried by
studying with stains or withPCR of the tissue to look at the
nucleic acids of an organism.
That would not be necessarilyvisualized on imaging studies.

(27:43):
And then we can look at themolecules, the receptors that
brains have on the cells haveand the relationships of the
major cell types the neurons,the glia, the blood vessels in a
very different, oftentwo-dimensional way, but, in
terms of a molecular analysis,in a much more in-depth way than

(28:08):
you can with imaging studies orbiofluids.
There is certainly value,though, because when we're
looking at a brain it's at onestage of disease, it's a
one-time point.
By having those other studiesbeforehand biomarkers of imaging

(28:28):
or biomarkers of biofluids youcan do longitudinal studies, and
I'm involved in a lot of thosefor various different diseases
as well, specifically with ALS,where we have a large
multi-institutional study to tryto have a large

(28:50):
multi-institutional study to tryto enroll every patient with
ALS.
It's an audacious study thatjust started a year or two ago,
but the idea is to study themand work with them so that they
get access to large multi-centerclinical groups and that they
can participate in research tounderstand their disease.
This is a big undertaking for alot of areas of medicine.

(29:11):
Right now we're in the data era, we're in the information data
era, and having large numbers ofdata points is essential to
trying to understand our verycomplex species.
So we are a very diverse groupof people and everybody's
biology and everybody's diseaseand condition and how they go

(29:34):
through life and whatmedications they're on and what
they eat.
We're all different, so we'renot lab animals, we are
individuals, and sounderstanding the complexities
of disease and how it affectsone person versus another really
relies on studying many, manypeople.
So people who volunteer forclinical trials and people who

(29:56):
volunteer to donate tissues arereally helping out humankind, I
think, in a very, very specialway.
That allows scientists andclinicians to get better and
better at providing new ideas ofmechanisms of disease and
potential targets for therapy.

(30:18):
So I think that's maybe thebeginning of answering the
question, but I might need youto remind me of the question
again.
I got a little off target.

Speaker 1 (30:29):
No, actually I think you're pretty much right on
target.
I'll just ask a couple of otherfollow-up questions.
So we're going to be talkingabout PANDAS and PANS and other
neuroimmune disorders and I'mwondering if you can discuss
this sort of macro question.

(30:49):
We know from the clinicalsymptoms of those with PANDAS
and PANS.
We have an idea that thosesymptoms are emerging from
activity that's going on in thebasal ganglia.

(31:09):
And how do we know that?
Well, we know that because, say, parkinson's disease has with
some similar symptoms and youcan probably elaborate on this.
The research has been done onthat and we know that a lot of
the issues surface in the basalganglia and you can provide some

(31:29):
better examples, I'm sure, butwe don't know for sure.
So with studying postmortembrain tissue, you can confirm or
not confirm that it is largelythe problems are taking place in
the basal ganglia.
Is that in a very macro sense?

(31:50):
And then you can home in onwhat's going on on a much more
micro sense, because we don'tknow why those the symptoms that
we call pand or PANS.
We don't know exactly theunderlying mechanisms that
produce those symptoms.

(32:12):
So eventually I hope that bystudying brain tissue we can get
to the second part, but wecould definitely and I think you
have gotten to the first partof where is the action in the
brain that's leading to thesesymptoms?
Am I?

Speaker 3 (32:28):
Yeah, that's absolutely correct.
So neurologists are alwaystrying to pinpoint where in the
brain and multiple places in thebrain certain neurologic
diseases occur.
Same with psychiatry andneurosurgery.
Understanding the normalfunction of the brain has gone
on now for hundreds of years,and more specifically in the

(32:52):
last 50 years, to get a betterfeel for what areas of the brain
control what aspects of ourcomplex life, and then trying to
understand if it's one areathat is affected.
And I got very interested inneurodegenerative diseases and
there are some overlaps inneurodegeneration of mechanisms.

(33:15):
But then it always struck me asbeing fascinating by why in
this one neurodegenerativedisease like Parkinson's disease
do we lose dopaminergic neuronsin the substantia nigra?
And why is it in Alzheimer'sdisease that we get plaques and
tangles predominantly in thelimbic system, in the

(33:37):
hippocampus and in the frontallobe, but other areas are kind
of spared?
And in ALS, you know why is itthat these motor neurons that
control our skeletal musclemovement in the brain and the
spinal cord degenerate but otherareas we think are not as
affected?
If you do very careful testingof all of these

(33:59):
neurodegenerative diseases youdo find areas that maybe aren't
as affected as the primary areabut also have changes.
So that always struck me asbeing very interesting, and
having the ability to not justlook under the microscope at
cells but to understand theneurotransmitters and the

(34:24):
receptors that are all differentin all different areas and the
communication that happensbetween neurons and glial cells
is different in different areasallows you to start thinking
about targets for intervening,whether or not you're
intervening by surgery to takesomething out.

(34:45):
You might be intervening withelectrodes and deep brain
stimulation of somebody withParkinson's disease to activate
a very specific area of thebrain for function, or you might
be using drugs that interactwith specific receptors in
specific areas of the brain totreat a neuropsychiatric disease

(35:09):
.
So those are all areas where welearn.
You know collectively asneuroscientists what the
function, normal function, is,and then we study, as
neuroscientists who studydisease, as neuroscientists who
study disease, what happens inthose areas?
Is it a loss of a cell type?

(35:29):
Is it an upregulation or adownregulation of a specific
receptor or a second messengersystem within cells?
That is the detriment and Ithink pathologists are focusing
primarily on where's the damageto the brain and is it a

(35:51):
regional area of the brain or isit a receptor or a genetic
change to that cell?
Is it a neuroinflammatorychange, and so you brought up
the disease and conditionPANS-PANDAS, where you know the
basal ganglia, as you said wethink, is affected and we know

(36:13):
that because of the clinicalsigns and symptoms that patients
with this disease have.
But we also know it becausepeople with the disease and
condition get image studies.
Know it because people with thedisease and condition get image
studies and there are researchstudies to show that there are
changes in the basal gangliathat the neuroradiologists can

(36:34):
read as a difference in thatarea.
So to then be able to take thatinformation from what the
clinicians know the signs andsymptoms to what the
neuroradiologists can tell you,from the imaging studies to then
what we find actually in thebrain at autopsy, is sort of the
full circle of trying tounderstand and confirming our

(36:57):
thought processes.
Now the reality is, what I seeunder the microscope is the tip
of the iceberg, and so many manydiseases, unless it's a
localized cancer or a localizedinfection in a certain area of
the brain, involve multipleareas of the brain.
The circuitry of the brain isbeing discovered now and the

(37:19):
understanding of pathways ofcommunication in the brain and
detriments to that very complexcircuitry are being understood
in certain diseases, but westill have a long way to go, I
think.
And so in conditions like PANSand PANDAS, I think it's a newly

(37:41):
discovered disease entity.
Certainly I'm sure it's beenaround for a long time and it
was just not recognized.
I certainly didn't learn aboutit in medical school when I was
in the 80s and 90s, and didn'tlearn about it much even in my
residency, because nobody hadever looked at a brain from

(38:02):
somebody with pans and pandas.
So it wasn't in theneuropathology literature.
So the understanding of eithernew diseases or new entities can
benefit tremendously fromunderstanding at the tissue
level and the cell level and themolecular level, and we can't

(38:24):
do that if we don't havematerial to look at.

Speaker 1 (38:28):
Wow, well, that's kind of a good segue to talk a
little bit about the POND brainbank.
Pond is the acronym for PANDAS,pans and other neuroimmune
disorders, pond, and youestablished that in January of
2022, if I recall correctly.

Speaker 3 (38:50):
Right before COVID I think Right, yeah, or was it
right after COVID?
No, it was actually right afterCOVID.

Speaker 1 (38:58):
Oh, you're right, You're right I think so Because
I remember we just a bit of abackground here when our
daughter died, we were asked ifwe would consider donating her
brain to one of the brain banksat the National Institute of
Mental Health, nimh, which wedid, and then, for a variety of

(39:22):
reasons, we decided that itwould be a better idea to move
her brain, and I knew Dr JimGiordano, who is a neuroethicist
at Georgetown UniversityActually, he's the chief of
neuroethics, the neuroethicsstudies program, and a professor

(39:43):
in neurology and, I think,biochemistry, and he wears a
number of other hats.
Anyway, I was acquainted withhim through my daughter, alex
Manfel, and he suggested that Ispeak with you to see if you
might be interested and inclinedto accept her brain.

(40:05):
So we did that before January2022.
I think it was just beforeCOVID.
Yeah, because they actuallydidn't move her brain until
pretty much after COVID, if Irecall correctly.
I know that I am very gratefulthat you said yes, and there's a
whole community of people whoare very grateful that you said
yes, and there's a wholecommunity of people who are very

(40:26):
grateful that you said yes.
You would be interested inlearning more about pandas and
pants, because I don't know thatyou've emphasized what a strong
interest you had in the role ofneuroinflammation in some of
these disorders that you wereinterested in, so you

(40:46):
established this with the helpof the Alex Banfield Fund.
I'll quickly add Since thattime there have been sadly more
brains that have been added tothe repository.
How many do you have now?
12?
.

Speaker 3 (41:04):
We have nine brains in the bank right now, and so
we've been in existence for twoor three years, and nine folks
have made the decision familieshave made the decision that they
learned about the Pond BrainBank and there are not too many
others like it around the worldthat this would be a good

(41:26):
repository to be able to kind oftake the tragedies that have
occurred and make something goodand try to learn from them.

Speaker 1 (41:38):
So there has been one study that has been published
based on one of the brains,which happens to be Alex.
In that study, this brain wasexamined very closely and you
had access to the clinicalinformation, which I think

(41:59):
enriched the neuropathologicalinformation, and I'm wondering
if we can talk a little bitabout that.
A good starting point might bewhat it was that you examined,
so that people understand that.

Speaker 3 (42:17):
Yeah, so this was several years ago, not that many
.
I met with you and your husbandand we talked a little bit
about how our brain bank and mypersonal interests in
neuroinflammation might bebeneficial to starting a bank
that, as I said earlier, wereally had no idea about the

(42:39):
neuropathological findings inthis disease and in this
condition, findings in thisdisease and in this condition,
and thankfully not too manypeople die from this disease.
I mean, you know I think you'vehad others on your podcast that
have talked more eloquentlythan I can about the
epidemiology of pans and pandasand the prevalence worldwide

(43:01):
worldwide.
But in the situations wheresomebody does die, having the
tissue available for closeexamination and then for
research distribution is, Ithink, essential to
understanding more about theparticular disease.

(43:21):
So I decided, together with myinstitution, that we would like
to begin bank that dedicatedcollection specifically for PANS
and PANDAS, but recognize thatother neuroimmune diseases and
there are quite a few of themdon't often make it into brain
banks either either, and thatthere are researchers who very

(43:51):
much need to have these tissuesbecause we don't get biopsies,
as I said before to be able toform ideas and hypotheses about
the disease and then take thatinformation, even if it's from
one case study, back to thelaboratory, to ask questions in
animal models and working withpatients to have clinical trials

(44:11):
for understanding these complexand turns out in some cases
very preventable diseases.
So I agreed to start the bankand to serve as a custodian for
tissues and let the communityknow and let a variety of other

(44:32):
folks that might come acrossdeaths in this condition know
about this, so that we couldlearn more about whether there
are similarities or differencesin PANS and PANDAS, because
that's as important in diseaseunderstanding, because you might
have different treatments fordifferent diseases, they might

(44:54):
be very different kinds ofdiseases and then to retain the
tissues and have a robust waythat scientists who wanted to
get access to the clinical andpathological data we call it
clinical pathologic correlationor clinical pathologic
information, again in ade-identified manner they would

(45:16):
have access to that and theycould query that information and
ask their scientific question.
And so we did begin it in 2022.
And over the last two or threeyears we've had both adults,
children, young adults and acouple of older adults who may
have had this condition for along period of time and their

(45:41):
families wanting to make thedonation to the bank.

Speaker 1 (45:44):
So can we talk a little bit about about what you
found and going through thepaper and I will provide the the
reference for this on thepodcast website.
I'll provide the reference forthis you found mild gliosis and
and Alzheimer's type twoastrocytes.

(46:08):
Can you talk a little bit aboutwhat gliosis is?

Speaker 3 (46:11):
The two major kinds of cells that we have in the
brain are really not just twocell types, but the large
umbrella category are calledneurons and glia, and most
people, I think, are calledneurons and glia and most people
, I think, have heard of neuronsbefore.
They're kind of the activechemical, electrical cells that

(46:32):
communicate with each other andform synapses and allow us to do
all of the things that we'redoing throughout the day Glial
cells glia is Latin for glue,and so the early microscopists
actually, who studied thesecells under the microscope,
found them and said well, thesearen't neurons.

(46:53):
They look different, they'redifferent sizes and shapes and
they're kind of surroundingneurons.
They're similar, and so theythought maybe they're the glue
that sort of holds the braintogether, so they called them
glial cells.
We now know that, just likethere are multiple different
kinds of neurons that havedifferent neurotransmitters and

(47:13):
have lots of different functions, there are lots of different
kinds of glial cells or a fewdifferent kinds of glial cells,
and they probably are differentin different regions and they
are in close proximity toneurons in different regions and
they are in close proximity toneurons.
We say that you know, a regionof cells in the tissue is a
neighborhood and thatneighborhood has neurons, glial

(47:37):
cells, blood vessel cells, andit's bathed in CSF and those
cells are all communicating witheach other to be able to do the
important things in theneighborhood.

(48:01):
And if there is a problem, adisease that happens, it
probably affects all of thecells to some degree.
In this complex neighborhoodit's not usually just one cell
type that gets injured orchanges neighborhood, it's not
usually just one cell type thatgets injured or changes.
When there's an injury, there'sgoing to be a reactive change
to that injury and one of thefunctions, one of the types of
glial cells, is called anastrocyte, and astrocytes have
many different factors.

(48:22):
They buffer potassium, they areat synapses and often situated
around nodes of Ranvier, andthey recycle neurotransmitters.
Neurodegeneration, infection,stroke is that they become

(48:47):
reactive that's, in quotations,reactive and they change their
shape, they change the moleculesand the things that are inside
them and they have the abilityto put out long processes to be
able to interact with the areaof injury.
Sometimes they wall off areasof injury, and so gliosis is a

(49:12):
generalized term that we usewhen there is a traumatic or
pathologic process happening ina certain area of the brain that
has gotten the astrocytesrevved up to do something.

Speaker 1 (49:27):
Okay, so there was evidence of this mild gliosis
found in this brain.
Just to review.
So the glial cells you saidthere are several, there's
astrocytes, there's microglia,right?

Speaker 3 (49:41):
Microglia is another type of.
They're sort of the residentimmune cells within the brain.
They actually migrate into thebrain from our bone marrow
immune cells during developmentand then they stay put and they
have a lot of similarities tolymphocytes and macrophages in

(50:02):
the rest of the body.
And then the other cell type,other glial, major glial cell
type, is the oligodendrocyte,and they are important also in
communicating with neurons andmaking the myelin that enwraps
the axons within neurons.

(50:22):
But they also have metabolicregulatory functions as well.

Speaker 1 (50:26):
But they also have metabolic regulatory functions
as well.
So with all of them they haveregulatory functions.
But there are positive thingsthat the gliosomes are doing,
absolutely.

Speaker 3 (50:35):
They do help to maintain a healthy neighborhood.

Speaker 1 (50:38):
Okay, so gliosis refers to a situation in the
brain in which it's no longerconsidered healthy.
Is that correct?

Speaker 3 (50:50):
There's a problem that's happening, yeah, and then
the glial cells are reacting tothat problem to try to help it,
and sometimes they're helpfuland sometimes they have a
hindrance to further support.
But they are reactive, likeyour immune system is reactive
to an infection, and too much ofan immune response can cause

(51:16):
damage to tissue and too muchswelling probably is not healthy
for the tissue and can preventrepair in some instances.

Speaker 1 (51:35):
So in this case you found the gliosis in the basal
ganglia, certainly in thecaudate nucleus in particular,
if I recall from the autopsy andfrom your paper, and the
thalamus as well.
Were there other areas that youfound here?

(51:57):
The temporal lobes, thehippocampus and the basal
ganglia show mild gliosis.
Did you expect that?

Speaker 3 (52:04):
Well, I didn't know what to expect.
This was the first brain thathad been looked at in this
condition, and so we sampledwidely because we didn't know
what to look for.
We had a good sense that fromother papers and things that
this was a neuroinflammatorydisease and probably mostly

(52:26):
related to antibodies that wereable to get into the brain that
were cross-reacting frominfectious disease and then
getting into the brain andcausing damage, either direct
damage or indirect damage, byinteracting with
neurotransmitters or receptors.

(52:46):
But we had really no idea whatto look for and so we did our
standard examination of samplingmany different areas of the
brain and then seeing what wesaw on the initial slides, and
then doing staining to furtherclarify what we suspected.

(53:08):
Or I would say you know what wecould identify with the stains
that we used.
And so in this case, thoseareas that you mentioned seem to
have the most degree of gliosis, specifically the caudate and
the putamen and the thalamus,and these are areas that are

(53:28):
important in lots of differentfunctions that we have movement,
but also they are attached tothe limbic system.
They are important inregulating hormone levels,
specifically in the thalamus andthen in the hippocampus, memory

(53:50):
and the temporal lobe, variousdifferent aspects of, I think
memory is the most important one.
So in those areas we foundgliosis and we also found mild
lymphocytic inflammation, foundmild lymphocytic inflammation,

(54:10):
and that was.
You know, both of those thingswere not completely surprising
to us but then required furtherstains to kind of try to
classify and to try tounderstand a little bit better.
The inflammation that we sawwas lymphocytic inflammation,
often around blood vessels, andwhen you look under the
microscope using our standardstains that we use for all areas

(54:31):
of pathology, called hematoxlinand Eosin or H&E stain, you can
recognize the lymphocyte andfrom a glial cell or from a
neuron, but you don't knowreally much about that
lymphocytes.
And the immune system is almostas complex as the nervous system
in that we have lots and lotsof different types of

(54:52):
lymphocytes that have manydifferent functions and the B
cells make our antibodies andthey interact together with the
T cells and macrophages thateither can come into the brain
from the periphery or microgliacan turn into macrophages.
So we wanted to firstcharacterize those lymphocytes,

(55:13):
those few lymphocytes that wesaw around blood vessels in
those areas, and we found thatthere were both B cells and T
cells, but predominantly T cells, and that was interesting to
learn about.
I'm not an immunologist and soI would say you know we still
have more research to do on theimmune cells that have come in

(55:35):
from the periphery.
You know, in these cases notjust in the first case but in
others as well but understanding, you know, the uniqueness of
the T cell response and the Bcells I think was one of the
things we talked about in thepaper, and we looked for a
different marker called CD25,which is a marker that's

(55:59):
important in regulating those Tcells and getting them to do
what they're supposed to do.
It's often studied in lymphomaand hematologic malignancies.
It's upregulated, but it may beimportant in neuroinflammatory
diseases as well in trying tounderstand, and so we wanted to

(56:22):
use that marker.
But there are still othermarkers and other areas of
investigation that people whoknow more about immunology have
started to look at with some ofthese tissues, have requested
the tissues and are looking atspecific receptors and immune
cells and trying to understandthings about this disease as
well.

(56:42):
I mentioned too that we thinkthat this is a disease that is
often caused by abnormal or toomany antibodies that are
produced against some of thebugs that people have infections
to that somehow get into thebrain or that the cells that
make the antibodies the B cells,the plasma cells get into the

(57:05):
brain and start makingantibodies that really aren't
supposed to be in the brain andthat there's some
cross-reactivity between theseantibodies and molecules in
either neurons or glial cells.
That then causes a derangement.
Unfortunately, neuropathologycan't really see the antibodies

(57:25):
and we don't have a greattechnique to be able to isolate
these specific abnormalantibodies in tissues people are
living by.
Either CSF or blood is animportant diagnostic thing that

(57:53):
can help to make the diagnosis,but unfortunately we can't.
We don't have a great techniqueto be able to look at specific
antibodies neuropathologically.

Speaker 1 (58:01):
You can look at the proteins, though.
Correct, you can look at theproteins though correct.

Speaker 3 (58:06):
You can measure in general proteins, yes.
You just can't ask the question, though are there specific
antibodies against, for example,streptococcus bacteria?
Because the unique aspect ofthat protein we don't have a

(58:28):
mechanistic way or anotherantibody that recognizes that
specific antibody.
So we can say that there areantibodies in the brain tissue
but not specific antibodies, ifthat kind of makes sense.
Antibodies, if that kind ofmakes sense.
So the diagnostic way of doingit is actually, or one of the

(58:54):
diagnostic ways of looking atautoimmune diseases and I'm not
sure if this is done still is totake CSF from somebody who has
a putative neuroimmune,antibody-related autoimmune
disease and take that antibodyand then look at animal tissues,
put that antibody on the animaltissues and see if it lights up
specific areas.
But we can't really if we don'thave the serum from somebody.

(59:16):
We don't know whether or notthose antibodies have sat down
on top of the other proteins inthe brain specifically to cause
an interaction.
And if there's somebody in theaudience who's listening to this
and knows a method of doingthat, please, please get in
contact with me, because Ihaven't been able to find a

(59:38):
technique that does thatpost-mortem.

Speaker 1 (59:41):
So there is some very interesting research that will
be brought to light pretty soon,in which the researcher was was
, through proteomics, trying toidentify a protein or proteins
that might be able to be used asa quote-unquote biomarker, and

(01:00:02):
so it looks promising, and thatmade me wonder whether we could
go back and look for thatprotein or those proteins in the
brain tissue.
Is that possible?

Speaker 3 (01:00:16):
That is possible.
Okay, and that's exactly whatyou know the purpose of having
the tissues available as newdiscoveries are made.
If you have a target and you'velearned a biomarker against
that target, you can go back andsee if that target is within
the tissues, either at theprotein level or if it's an RNA,

(01:00:39):
at the RNA level, to see ifit's expressed in a particular
cell type.
That is a possibility.

Speaker 1 (01:00:44):
Yes, Okay, okay, okay .
So the gliosis, just from areally layperson's kind of
standpoint.
And people, otherneuropathologists and I believe
you have too told me that youjust simply wouldn't expect to
find that much gliosis in a26-year-old, recognizing you're

(01:01:06):
probably not looking for gliosisin the average 26-year-old,
recognizing you're probably notlooking for gliosis in the
average 26-year-old, but stillis it safe to say that we
wouldn't expect to find thatmuch in a healthy 26-year-old?

Speaker 3 (01:01:20):
That's correct.
Yeah, if we don't have anotherreason for the gliosis.
We just wouldn't expect to seeit If the person didn't have a
tumor or a specific infection toan area or a stroke.
And younger people can have allof those things, but we didn't
see any of those findings inthat particular examination.

Speaker 1 (01:01:42):
So anything else you'd like to mention that you
found in this research?

Speaker 3 (01:01:48):
Well, we found similar findings in at least one
and maybe two other cases ofthe brain bank, and I think
that's important when you havenewly described cases, and so we
will probably have anotherpublication that will write up
on some of these findings.

(01:02:08):
We don't have frozen materialin all of the nine cases.
Sometimes we only have formalinfix paraffin embedded and we
can make slides from them.
But we can still examine fordifferent markers of immune
cells and for gliosis, and wehave been able to find that in a
couple of other cases.

Speaker 1 (01:02:29):
So how quickly does gliosis occur?
Is that something that can beanswered?

Speaker 3 (01:02:33):
Yeah, we usually think that the astrocytes react
within about a week of someproblem and that comes from
hypoxia, ischemia kind ofresearch, stroke kind of
research and also trauma.
Certainly things are happeningimmediately, but from what we

(01:02:55):
can see under the microscope andthe production of some of the
proteins that the glial cellsmake, we often don't see the
major changes for at least a fewdays under the microscope and a
little bit longer.
Now, if you measure changes toglial cells in experimental
models, they happen quicker thanthat.

(01:03:16):
But from what theneuropathologists can see for
gliosis I would say it's usuallyfive days to seven days is some
of the earliest changes that Isee.

Speaker 1 (01:03:27):
And can it be reversed?

Speaker 3 (01:03:30):
Yeah, I think it is a reversible finding in
neurologic disease that theastrocytes have this phenotype.
You know, astrocytes usuallyhave a regionality and don't
make a lot of a particularprotein called GFAP and that's
our marker for gliosis.
So we stain for GFAP to tell usthat there are gliotic cells,

(01:03:56):
and I think that most people,most neuroscientists, believe
that you don't become a glioticcell and then you die.
You probably have a decrease inthe amount of GFAP If the
problem goes away.
You don't have long-termchanges in all of the glial
cells.

(01:04:16):
Now, depending on what theinsult is, you can have
long-term permanent changes inglial cells and they can be
gliotic for forever, but that'susually in more severe things
like stroke or around braintumors.
I think the typical infectionsthat we get throughout our life,

(01:04:41):
the small bumps maybe have alimited gliosis.
That probably goes away.
So I don't see at the end oflife and I look at many, many,
many, many brains.
I don't see gliosis in peoplewho are in their 70s and 80s,
unless they've got other thingsgoing on.
So it's not a permanentcondition in my mind.

(01:05:01):
Okay, a permanent condition inmy mind.

Speaker 1 (01:05:05):
Okay, well, I think that this paper it's the first
study that results that havebeen published of an individual
with PANDAS or PANS, a firstclinical pathological study
that's been published so that wecan see what's going on in the

(01:05:27):
brain and also correlate that asmuch as possible with the
clinical history of thatindividual, this case being Alex
.
So it's one case study.
So there are limitations indrawing conclusions from case
studies, of course, but you'vejust indicated that there are a

(01:05:50):
couple of other.
You found similar informationin a couple of other brains or
brain tissue, correct?

Speaker 3 (01:05:59):
That's correct, yeah.

Speaker 1 (01:06:00):
Increases our confidence in the presence of
gliosis and some of the otherthings that you observed.
Do you have any any researchthat that you would like to see
done or that's uh in yourpipeline in this area?

Speaker 3 (01:06:17):
yeah, yeah.
So you know, as I said, my mymajor area of research is is
really in neurodegenerativediseases and and als, but I, but
I, you know I think mostneuropathologists like to study
multiple different things andwhen there is this interest of
something novel that reallyhasn't been looked at before.

(01:06:39):
I'm a team scientist and I lovecollaborating with people who
have great questions and that Ican help provide the person's
question and they write a smalldescription of their research

(01:07:13):
project and we send it to theBiospecimen Use Committee and
they make a decision.
Because I would say, at thispoint in time, we still,
depending on what they areasking, we still don't have lots
and lots of cases to be able togive material out, and so we're
guardians of this material butwe want to get it.
Every banker doesn't want tohave tissues and slides staying

(01:07:37):
in their bank, they want to getit out to researchers.
So I offer, you know, to be acollaborating scientist on just
about all of the you know, theprojects, that, the projects
that are requesting tissues,just because I can help,
especially as a neuropathologist, with understanding, imaging
and ways of staining tissues.

(01:07:57):
That can be very helpful.
So I think we need to furtherclarify the immune response, the
lymphocytic response.
I think that there are ways nowof in biology called spatial
profiling, where you can take apiece of tissue.

(01:08:18):
You can first look at it to knowthe region and know, you know,
the types of cells that are inthat tissue.
But then there are verysophisticated ways of saying, at
a single cell or a small groupof cells, you know what are
those cells making in terms ofproteins or RNA that might be

(01:08:39):
different in somebody you know,two or three or four people with
this condition in a specificarea, compared to two or three
or four people with thiscondition in a specific area,
compared to two or three or fourpeople that don't have this
condition.
Are there proteins that areupregulated, proteins that are
downregulated?
And so I think those kinds ofquestions really still need to
be done and we have thecapabilities of doing them now.

(01:09:01):
Those, in my mind, are reallyimportant.
And then I think the you knowthe queries of people that are
trying to understand veryspecific protein markers that
you mentioned earlier that theyfound as a biomarker, maybe from
biofluids, and then going backto our tissues and asking the

(01:09:22):
question you know what areas ofthe brain actually express these
specific proteins.
That might give us someinsights as well into what areas
of the brains are beingaffected in this particular
disease.

Speaker 1 (01:09:34):
Wow.
I think it's important to getthe word out there as much as we
can about the presence of thebrain bank, of the brain bank.
Of course, we hope.
That in my heart is that therewill be no more additions to the
pond brain bank, but if thereis a death that occurs, I would

(01:10:02):
like everyone to know about theexistence of this so that we can
learn more and be able toeffectively treat people with
these disorders.
That's our goal at the AlexManfield Fund.
So my final question, I guessunless you would like to add

(01:10:23):
something else that I haven'tthought of asking, or a question
I skipped- I think we'vecovered quite a bit Okay.
So I'm wondering you talk alittle bit about this in the
paper, so what doneuropathological reports like
this tell us about the need tochange the nomenclature?

(01:10:44):
To refresh the listener's mindPANDAS.
The P in PANDAS stands forpediatric autoimmune
neuropsychiatric disorderassociated with strep.
The P in PANS, which is thebroader category that
encompasses PANDAS.

(01:11:04):
The P there also stands forpediatric.
You just did a.
Your research was conducted ona 26-year-old and you mentioned
that there are people who areolder than who have had their
brains donated to the, to thePond Brain Bank.

(01:11:25):
What does that tell us aboutchanging that nomenclature?
You?

Speaker 3 (01:11:28):
know diseases get named for a variety of different
ways.
Finally, getting away from theresearcher who first studied
them and the disease beingcalled that I think in medicine
we're trying to have scientificnames for diseases.
I think the recognition thatyoung adults especially can get

(01:11:49):
this situation they getinfections just like the rest of
us is incredibly importantPrimary physicians as well as
psychiatrists as well asrheumatologists as well as
pediatricians, rheumatologistsas well as pediatricians that
this is a disease not just inthe pediatric population.

(01:12:10):
And I think the only way tomake people aware of it is to
study it more and to get moreNIH research to study the
epidemiology of the disease, tostudy pathology of the disease
and to do more clinical trialsfor people with the disease,

(01:12:31):
because we learn in each ofthose clinical trials of what
works and what doesn't work tohelp people down the road with
it.
So I do agree that we probablydo need better nomenclature and
better names for this for thescientific and clinical
community mostly for theclinical community so that they

(01:12:55):
keep their radar open and theirthoughts open about when
somebody asks them the rightquestions and to do the right
testing.
Maybe, if you get lucky andthat test comes through, then
you've got your diagnosis.
But in general, primary carephysicians are among the
smartest and, to me, the mostrespected physicians we've got,

(01:13:17):
and it's not just physicians,it's PAs, it's nurse
practitioners and all clinicalcare folks that are working with
people with large numbers ofpeople.
A friend of my son who's achild psychologist and I asked
her she had learned about it andshe said yeah, I, you know, I
just had a course that mentionedthat she.

(01:13:37):
She said yeah, I actually thinkI might have had a patient with
this and I talked with thefamily about it and so it is
getting more recognition.
But it is incumbent upon thepeople who are studying it in
medical schools to make sure andnursing schools that they are

(01:13:58):
teaching about this.
And I've incorporated now inone or two of my lectures with
the medical students about theseconditions and we talk about it
amongst other neuroimmuneconditions.

Speaker 1 (01:14:12):
That's great and I know, with the fellowship funds
that the Alex Manfield Fund hasprovided to Georgetown in the
neurology department, then Ithink that it's going to be
included in many more curriculaas well.

(01:14:32):
So, brent, thank you foreverything you do and including
this podcast interview.
We are all very grateful.
I think you're really a keymember of the team helping to
move understanding of thisdisorder forward so that we can

(01:14:52):
identify the best treatments andhow to diagnose this more
effectively.
Thank you very much.

Speaker 3 (01:15:00):
Thank you, and thank you to the Alex Manful
Foundation and your family forentrusting us, for allowing us
to help get these importantfindings and tissues out to the
wider scientific community.

Speaker 1 (01:15:13):
Thank you for those words.
Thank you, okay, that's a wrap.

Speaker 2 (01:15:20):
This concludes episode 12 of Untangling Pandas
and Pans.
Thank you for listening.
Please continue listening for apersonal message from Susan
Manful.

Speaker 1 (01:15:34):
Brain donation is a powerful act of love, ensuring
that your loved one's legacylives on through groundbreaking
discoveries.
If you've lost someone to aneuroimmune disorder, consider
this gift of hope.
Learn more about how you canmake a difference by visiting

(01:15:55):
our website,wwwthealexmanfulfundorg and
clicking on the Pond Brain Bank.

Speaker 2 (01:16:13):
For more information about Pandas and Pans and the
Alex Manful Fund, please visitthealexmanfulfundorg.
The content in this podcast isnot a substitute for
professional medical advice,diagnosis or treatment.

(01:16:35):
Always seek the advice of yourphysician or other qualified
healthcare provider with anyquestions you may have regarding
a medical condition.