Inpt/CL docs: Anyong doing anti-NMDA receptor Ab workups for new onset psychosis?

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fiatslug

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I've just started working in child/adolescent psychiatry inpt again. We don't have a pediatric unit at my hospital/not affiliated with a university, so I don't know how much enthusiasm I can whip up for a fishing expedition. The last spinal tap I did (though: champagne tap, and on a 6 week old, b*tches!) was cough cough several years ago. Just wondering if any units are doing this now as part of new onset psychosis w/u. I have a pt who (in an ideal world) I'd like to get this done on, if only because it's pretty sudden onset, no real fam hx of psychosis, and a remote hx of sz x1 (3 yrs ago). No real focal neurologic sx currently, except severe psychosis. She's 16 :(

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I don't think its typical to do that here if they seem otherwise healthy, but that being said as a medstudent I remember that on peds, IM and neuro there were several separate cases presented in grandrounds/M&M/etc. of anti-NMDA cases coming through our psych floor during that year that took awhile to be recognized and were eventually figured out on IM/Peds/Neuro after the patient destabilized medically and had to get transferred.
 
I have a deep suspicion that if we made this a standard of practice, we would find it A LOT.

If you don't look for it, you won't find it. And psychotic patients are not particularly good historians.

Just my clinical hunch, which is worth less than an anecdote :D
 
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I had some teenage peds patients for whom we consulted psych for new-onset psychosis, and the anti-NDMA was definitely part of their work up despite lack of other symptoms/hx specifically pointing in that direction. N=2 for whatever that's worth.
 
I order it on all new psychosis. There isn't much evidence for it to be honest - a lot of the more recent studies are finding similar positive rates in both patient and control samples. That said, anectdotally have had a positive result in 2 of the most unwell patients I've seen (that didnt have clear neurological features), who made an almost complete recovery with plasmapheresis and steroids without any antipsychotic treatment. My reasoning is it doesn't cost that much (£50) where I am, and I'd want it done if it was my family member that went psychotic.
 
A lot of the attendings at my institution have been starting to order serum anti-NMDA antibody on patients with anything other than a classic presentation of new-onset psychosis. I usually also try to get it in patients with history of ovarian masses and people who have catatonia that doesn't quite fit the expected picture of catatonia. The serum antibody is pretty sensitive - I've only ordered the CSF antibody if we were already tapping the patient for some other reason. Otherwise, I don't think it's necessary to subject the patient to a more invasive test (especially if they're acutely psychotic - I can imagine the types of delusions that one might form about an LP) unless they have a classic presentation of anti-NMDA encephalitis, which hasn't happened on our inpatient unit or our C/L service ever since our lab started testing for anti-NMDA antibodies about a year ago.
Also, we probably have a lower threshold at our institution because our lab is one of the few ones that does actually run the test, so it's less expensive and faster turnaround.
 
I've just started working in child/adolescent psychiatry inpt again. We don't have a pediatric unit at my hospital/not affiliated with a university, so I don't know how much enthusiasm I can whip up for a fishing expedition. The last spinal tap I did (though: champagne tap, and on a 6 week old, b*tches!) was cough cough several years ago. Just wondering if any units are doing this now as part of new onset psychosis w/u. I have a pt who (in an ideal world) I'd like to get this done on, if only because it's pretty sudden onset, no real fam hx of psychosis, and a remote hx of sz x1 (3 yrs ago). No real focal neurologic sx currently, except severe psychosis. She's 16 :(

Since NMDAr encephalitis has been in the literature all of 10 years, I don't believe you can make definitive statements about presentations. For example, there have been both acute and subacute onsets, purely psychiatric manifestations (~5%) as well as those with the "classic" syndrome of dyskinesia, altered level of consciousness, etc. Often, the behavioral/psychotic symptoms will present first and then progress into the autonomic structures as inflammation spreads. By then, the patient will be off your floor and into the ICU.

That being said, its also worth checking to see if the patient had any flu-like symptoms, as there's often a prodrome that might have flown under the radar. The CSF would be nice, since it would let you test generally for encephalitis/inflammation, HSVE, etc, its significantly more sensitive than the serum test (100% vs. ~85%) and can be a better predictor of prognosis/severity. If you're going to be spending the money and you can physically get the tap, I'd go for that. Otherwise, you won't be left standing there wondering if you're the 15% that had a false negative.
 
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I have a deep suspicion that if we made this a standard of practice, we would find it A LOT.

If you don't look for it, you won't find it. And psychotic patients are not particularly good historians.

Just my clinical hunch, which is worth less than an anecdote :D

I think so too, frankly. Now I'm just trying to figure out how to order the serum labs in Epic...
 
what is your reasoning for wanting to consider limbic encephalitis? Doesn't sound like she has had seizures, dyskinesias, or cognitive problems, clouding of consciousness, emotional lability etc? If this is really sudden onset that wouldn't really be consistent with the subacute presentation of limbic encephalitis. And you would be having a much wider differential and need to do a fairly extensive workup.

She is having a *lot* of emotional lability, seeming quite childlike at times (and in fact is losing it as I type). The only outliers thus far in the usual w/u is elevated IgG titers for Rubella (and that only got ordered because I hit the obstetrics panel lab when I started looking for VDRL ;)) and very low Vitamin D (5.4 3 weeks ago, replacing at 50000 IU weekly, will re-check). However, this is the PNW, and that's not an uncommonly low finding here...
 
they're send out labs at my facility. Will get anti NMDA receptor Ab as well as a paraneoplastic panel.
Last time I checked, I think there were only 3-4 labs in the US that do the test. But anti-NMDA costs $300 at my facility and a paraneoplastic panel costs $7000, so I try not to order a full paraneoplastic panel unless I'm suspecting something weird.
 
if you are just looking for NMDAR limbic encephalitis you are opening yourself up to liability if the patient does have an organic psychosis. There is never a justification for just ordering an NMDAR Ab - who is to say that a limbic encephalitis isn't caused by AMPA antibodies or VGKC antibodies or GAD antibodies etc? If you really think this patient has an organic psychosis then she needs to be a pediatric unit, or neurology should be consulted as the hospital will eat the cost for all these things (my understanding is psychiatry can't bill for any of these investigations inpatient). But essentially you need to be doing a MRI brain w/ w/o contrast with DWI, CT abdomen and pelvis, EEG, get some CSF - check for viruses, cryptococcus, HIV, and check Vit E, CRP, ESR, ANA w/ reflexive panel, ANCA, SSA/B antibodies, C3, C4, check anti-thyroid antibodies, RF, ceruloplasmin etc etc.

It has become a bit faddish to consider NMDAR limbic encephalitis amongst psychiatrist but there are many other things that must also be considered.
 
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I've done it twice. I reserve it for cases that are just out there such as an older man in his 60s with no dementia history, no progression of memory problems all of a sudden becoming psychotic with no prior psychosis or mania.

The test was negative but other antibodies associated with psychosis such as Lupus anticoagulant were (+). The case ended up getting published.
http://cpnp.org/resource/mhc/2013/11/antiphospholipid-antibody-syndrome-presenting-psychosis

And when I ordered the tests, the head of the lab called me up and started screaming at me-literally. It was like a little kid screaming, and I knew the guy couldn't get me fired, so I was pretty much like "ahem" while he screamed. A bunch of other people were staring at us, one doc screaming at me, and the entire time I'm just staring at him telling him calmly why I needed the labs.

What happened there was the lab told me they needed the head guy to give permission before they were done. Fine-I get it. Problem was the guy didn't give a response for 6 days, (only 1 day would've been excusable given the bureaucracy and such) all the while it's costing the system about $1500/day just to keep the guy in the hospital, so if that guy was so concerned about saving $10,000, he wasted almost the same amount by not responding to me.

I also called the guy about 3x a day (only to get someone else in the lab), left him e-mails, and still no response. In fact I think the main reason why he screamed at me the first time was because I took it up to the patient's rights department (AKA Patient Relations) because the family was getting stuck with the bill and I believed their right to cost-effective treatment was being spurred. When he found out I went to a third party he freaked out on me and part of his screaming was telling me how unprofessional I was for reporting him as not responding to me.

(I of course reminded him that his lack of response cost $7500 while he screamed that I was wasting money. If only I could've played this sound effect after I said that).


Yeah I got his point but this was a majorly weird case that warranted it IMHO if you actually give a damn. I go through hundreds of cases a year in inpatient and to only order the really weird labs about once a year IMHO doesn't point me out as a money waster. Plus each time I ordered the damn things we got a (+) that led us in a clinical direction and we had significant reason to believe they were playing a factor in the psychosis.

IMHO you only order the stuff when you see some very atypical signs not explainable by the obvious and order the more common labs first. Do not order anything extraneous unless there's good reason. Students-don't order labs just to satisfy an academic curiosity.
 
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if you are just looking for NMDAR limbic encephalitis you are opening yourself up to liability if the patient does have an organic psychosis. There is never a justification for just ordering an NMDAR Ab - who is to say that a limbic encephalitis isn't caused by AMPA antibodies or VGKC antibodies or GAD antibodies etc? If you really think this patient has an organic psychosis then she needs to be a pediatric unit, or neurology should be consulted as the hospital will eat the cost for all these things (my understanding is psychiatry can't bill for any of these investigations inpatient). But essentially you need to be doing a MRI brain w/ w/o contrast with DWI, CT abdomen and pelvis, EEG, get some CSF - check for viruses, cryptococcus, HIV, and check Vit E, CRP, ESR, ANA w/ reflexive panel, ANCA, SSA/B antibodies, C3, C4, check anti-thyroid antibodies, RF, ceruloplasmin etc etc.

It has become a bit faddish to consider NMDAR limbic encephalitis amongst psychiatrist but there are many other things that must also be considered.

We do a similar workup not infrequently, albiet with a pretty heavy neuropsychiatry bias at my institution. We have even started IVIG on a patient on the psychiatry floor when neurology refused after a positive paraneoplastic panel and the pt went from catatonic with feeds to near return to baseline in the span of a week. We also strike out with these fairly extensive workups not infrequently but there is a clear limit to what we can test/find and I believe a number of cases that look like "organic" psychosis are and we just dont have the measures to test. These pts are often on the neuro service but we also house the more unstable ones on a locked psychiatry unit and have neurology on consult.
 
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we check occasionally at my institution, it doesn't hurt, but naturally this is obviously after other extensive work up has been tried and patient is same/worse/ not improving,
 
We have even started IVIG on a patient on the psychiatry floor when neurology refused after a positive paraneoplastic panel and the pt went from catatonic with feeds to near return to baseline in the span of a week.
wow, that must have been amazing to see
 
wow, that must have been amazing to see

It was incredible, the patient was scheduled to be sent to hospice, pretty rare to literally save a life in psychiatry. Almost every resident knew about the case and even our head of neuropsychiatry was moved.
 
if you are just looking for NMDAR limbic encephalitis you are opening yourself up to liability if the patient does have an organic psychosis. There is never a justification for just ordering an NMDAR Ab - who is to say that a limbic encephalitis isn't caused by AMPA antibodies or VGKC antibodies or GAD antibodies etc? If you really think this patient has an organic psychosis then she needs to be a pediatric unit, or neurology should be consulted as the hospital will eat the cost for all these things (my understanding is psychiatry can't bill for any of these investigations inpatient). But essentially you need to be doing a MRI brain w/ w/o contrast with DWI, CT abdomen and pelvis, EEG, get some CSF - check for viruses, cryptococcus, HIV, and check Vit E, CRP, ESR, ANA w/ reflexive panel, ANCA, SSA/B antibodies, C3, C4, check anti-thyroid antibodies, RF, ceruloplasmin etc etc.

It has become a bit faddish to consider NMDAR limbic encephalitis amongst psychiatrist but there are many other things that must also be considered.

I had to reopen this thread because I LOVE this post! The NMDA fad has become ridiculous; some psychiatrists will use any excuse to order it. Just because its mechanistically linked to a biological hypothesis of schizophrenia and was sensationalized in a book does not justify ordering the test for any young female with new onset psychiatric symptoms (which happens btw). The last thing I want is parents who read Brain on Fire insisting that I order the test (and threatening to get their non MD hospital administrator friends involved when I explain that its not indicated) when I have zero degree of clinical suspicion. As Splik pointed out, if I am considering NMDAR encephalitis, I need to be thinking about other "organic" causes of psychiatric symptoms, and I would probably consult neuro for the complete workup (most is mentioned in Splik's thread) just so I am not missing anything.
 
Speaking of NMDA stuff, at the jail I'm working at, I can order pretty much anything, even anything you'd find at a GNC. So I can order N-Acetylcysteine that does have a growing body of data showing it could help with psych disorders across the board.

Only ordered it once so far. I'm not going to order it to get my freak-on. I'm only going to order it in cases where there's a good reason to order it. So far it was a patient that was treatment sensitive to almost everything. E.g. akathisia on Risperdal 2, Geodon 40 mg Q BID, Abilify 10 mg, and very bad psychosis where those dosages barely did anything. Tried Seroquel but his EKG went crazy on it. He's now on Zyprexa still with akathisia but at least to a degree he could tolerate it. Added N-Acetylcysteine along with Depakote to augment the antipsychotic and reduce akathisia.
 
30 year old female with no psych hx, no family psych hx, no substance abuse history, no other medical history presents with sudden onset of psychotic symptoms over two days after a two day 102F fever. Initially mute then rambling and loud on admission with episodes of mild tachycardia, and an episode of repetitive hand and head motions. Self resolved somewhat after some sleep, however still with soft, somewhat non-articulate speech that is hard to understand, and odd behavior (dancing to a TV tune at full blast when people are trying to talk to her).

Infection, Viral, Brain Mass, Stroke, Seizure, Inflammation, Toxic, head trauma etc all ruled out. Nothing found on MRI, done without contrast only. Neuro suggested Anti-Hu and Anti-NMDA, with tests still pending. My consult note also points out the other cell surface antibodies AMPA, GABA, VGKC. Medicine really really wants this patient in the psych ward because they're basically just sitting and twiddling their thumbs. I'm telling them no way. Thoughts on any of it.
 
Thyroid function status? TPO/TG Ab? Paraneoplastic panel? Tox screen? Creatine kinase? ESR? Heavy metal screen?

Can you describe the hand/head motions? Symmetrical or asymmetrical? No trunk or L/L involvement at all? Fever subsided spontaneously after 2 days?
 
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Thyroid function status? TPO/TG Ab? Paraneoplastic panel? Tox screen? Creatine kinase? ESR? Heavy metal screen?

Can you describe the hand/head motions? Symmetrical or asymmetrical? No trunk or L/L involvement at all? Fever subsided spontaneously after 2 days?

Agree with this though I'm guessing ESR would have already been ordered. Definitely need a complete CSF paraneoplastic workup. Also need to do a more extensive UDS that picks up rarer things. Also would redo the MRI WITH contrast. If the workup was initially done systematically with nothing found, it's time to look for Zebras.
 
30 year old female with no psych hx, no family psych hx, no substance abuse history, no other medical history presents with sudden onset of psychotic symptoms over two days after a two day 102F fever. Initially mute then rambling and loud on admission with episodes of mild tachycardia, and an episode of repetitive hand and head motions. Self resolved somewhat after some sleep, however still with soft, somewhat non-articulate speech that is hard to understand, and odd behavior (dancing to a TV tune at full blast when people are trying to talk to her).

Infection, Viral, Brain Mass, Stroke, Seizure, Inflammation, Toxic, head trauma etc all ruled out. Nothing found on MRI, done without contrast only. Neuro suggested Anti-Hu and Anti-NMDA, with tests still pending. My consult note also points out the other cell surface antibodies AMPA, GABA, VGKC. Medicine really really wants this patient in the psych ward because they're basically just sitting and twiddling their thumbs. I'm telling them no way. Thoughts on any of it.

This is a weird case to do an MRI without contrast on unless they are doing it acutely for a stroke. Many of the things you mentioned really need MRI w/ contrast for me to be satisfied with. I presume there's been an LP that has normal findings and send out labs pending for all the Zebras paraneoplastic? Definitely want as much of an autoimmune workup as possible, at least ANA panel.
 
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In these conversations people often mention something about not only checking NMDA, but IIRC at my institution its an all or nothing thing w/ CSF paraneoplastic/antibodies, you just order the whole panel and couldn't pick and choose. Is that typical?
 
In these conversations people often mention something about not only checking NMDA, but IIRC at my institution its an all or nothing thing w/ CSF paraneoplastic/antibodies, you just order the whole panel and couldn't pick and choose. Is that typical?

The NMDA SERUM sample has become en vogue in psychiatry as a screening test. My opinion is that this is a fad because the disease was sensationalized in a book and the mechanism is academically interesting and related to schizophrenia
 
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