Medic_90x

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60 year old female with schizoaffective disorder on clozapine and lithium + other meds who is pretty functional and relatively normal at baseline. Has a one week history of episodes of weakness, "spasms" and falls. Comes into the ED with AMS, dysarthria and weakness. Afebrile. 3-4/5 strength.
Head CT and MRI are negative. Labs negative, except elevated wbc (but chronic, over 2 decades of lymphocytosis). Chest x ray shows ground glass opacities b/l. Urine is normal.
Treated with antibiotics for possible pneumonia. Rispideral discontinued, benzos discontinued.

Over the next week, patient waxes and wanes but is confused intermittently and cannot ambulate. Forgets questions etc. Strength is more 4/5-5.
More testing is done. CRP/ESR are normal. Rheum tests return normal except very positive ANA and positive ANCA. Anti-tpo negative. TSH wnl, on levo for hx of hypoT. HepC,HIV,HepB negative. Lithium levels normal. Clozapine level returns quite high, which could be an explanation but patient waxes and wanes + a dose was held with no relief.
EEG shows encephalopathy. LP is pending, cant get consent.

What's your differential with this patient at this point?
 
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jdh71

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Finish the rheum work up. Have rads relook at the brain MRI - ask about MRA/CTA brain/head/neck. Get a CT of the chest and start looking for potential biopsy targets.

Kind of weird that clinically significant neuro symptoms are present in a flaring rheumatological disease with a normal ESR and CRP. May need an LP it’s WNV season and it’s been relatively neuroinvasive this year plus EEEV has been a bigger deal this year too killed five so far by the last report I saw.
 
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MedicineZ0Z

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Finish the rheum work up. Have rads relook at the brain MRI - ask about MRA/CTA brain/head/neck. Get a CT of the chest and start looking for potential biopsy targets.

Kind of weird that clinically significant neuro symptoms are present in a flaring rheumatological disease with a normal ESR and CRP. May need an LP it’s WNV season and it’s been relatively neuroinvasive this year plus EEEV has been a bigger deal this year too killed five so far by the last report I saw.
Interesting case OP.


What's your thought process behind the rheum workup? What else would you order for this patient
 

jdh71

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Interesting case OP.


What's your thought process behind the rheum workup? What else would you order for this patient
All you have here is a apparently a “very positive” ANA - I don’t know what “rheum tests return normal” means here. Would be nice to know the dilution ratio. We also need the specific extractable antigens (ENA) - things like scl-70, SSA/SSB, RNP, etc. Also need an anti double stranded DNA. We need to look for a specific diagnosis associated with the elevated ANA. The ANCA needs to also be specified at least to PR3 or MPO to start. And if not positive then send out for the weird stuff.
 

differentiating

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At what point in the timeline was the MRI done? Wondering if there’s utility in a repeat scan.

With encephalopathy, I’d also wonder about autoimmune encephalitis vs infection in addition to what’s been discussed above. It’s not as good as CSF, but it’d probably be worth getting the typical autoantibodies (such as anti-NMDA) in serum if that’s not available. Also would definitely consider WNV (west coast) and EEE (east coast) based on travel history, as mentioned earlier. HSV probably less likely without typical imaging.
 

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What do her labs look like, co2 , pH. Could anyone explain why a why a random Ana was triggered with a normal esr/crp ? What is her baseline respiratory status? Any muscle rigidity ? Hyper or hyporeflexia ? Etoh at home? Normal kidney function vs this admission, normal lithium levels compared to now.

I would be thinking of
Nms
Clonzipine od.
Lith tox
Etoh withdrawal.




Maybe a cancer syndrome related encephalopathy.
 
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Medic_90x

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At what point in the timeline was the MRI done? Wondering if there’s utility in a repeat scan.

With encephalopathy, I’d also wonder about autoimmune encephalitis vs infection in addition to what’s been discussed above. It’s not as good as CSF, but it’d probably be worth getting the typical autoantibodies (such as anti-NMDA) in serum if that’s not available. Also would definitely consider WNV (west coast) and EEE (east coast) based on travel history, as mentioned earlier. HSV probably less likely without typical imaging.
During admission. Patient has very limited travel altogether.
What do her labs look like, co2 , pH. Could anyone explain why a why a random Ana was triggered with a normal esr/crp ? What is her baseline respiratory status? Any muscle rigidity ? Hyper or hyporeflexia ? Etoh at home? Normal kidney function vs this admission, normal lithium levels compared to now.

I would be thinking of
Nms
Clonzipine od.
Lith tox
Etoh withdrawal.




Maybe a cancer syndrome related encephalopathy.
Entirely normal. Some hyperreflexia initially. No hx of etoh abuse. Kidneys normal. Li normal.
 
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LP (s far!) showing somewhat elevated protein and glucose. opening pressure was on the low side. Otherwise normal with lyme/hsv/ndma/west nile pending.
 

differentiating

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During admission. Patient has very limited travel altogether.

Entirely normal. Some hyperreflexia initially. No hx of etoh abuse. Kidneys normal. Li normal.
Then I’d think you’d want to repeat an MR as well - symptoms on presentation could indicate a stroke, and you could miss an ischemic stroke on MR if it’s too acute.

About the LP: that elevated protein makes me even more worried for some sort of autoantibody in the CSF - whether secondary to a rheum disorder, paraneoplastic, or an idiopathic autoimmune encephalitis of some sort. Infection less likely without a white count.
 
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Medic_90x

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Then I’d think you’d want to repeat an MR as well - symptoms on presentation could indicate a stroke, and you could miss an ischemic stroke on MR if it’s too acute.

About the LP: that elevated protein makes me even more worried for some sort of autoantibody in the CSF - whether secondary to a rheum disorder, paraneoplastic, or an idiopathic autoimmune encephalitis of some sort. Infection less likely without a white count.
Besides NMDA, and lyme/west nile - what else would you suspect in a totally afebrile patient?
Maybee meets some mild clinical criteria for anti-ampa but not really for the other paraneoplastic stuff.

Any specific rheum disorders that can cause this? All we have is positive ana/anca. Negative anti-jo.

BTW, at baseline the patient could walk and reasonably hold a convo (hx of schizo, delusions etc). Cannot ambulate during admission and the confusion/forgetfulness prevents her from holding a convo.

I do wonder, is prion disease a consideration or does a fully normal mri rule it out entirely???
 

differentiating

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Besides NMDA, and lyme/west nile - what else would you suspect in a totally afebrile patient?
Maybee meets some mild clinical criteria for anti-ampa but not really for the other paraneoplastic stuff.

Any specific rheum disorders that can cause this? All we have is positive ana/anca. Negative anti-jo.

BTW, at baseline the patient could walk and reasonably hold a convo (hx of schizo, delusions etc). Cannot ambulate during admission and the confusion/forgetfulness prevents her from holding a convo.

I do wonder, is prion disease a consideration or does a fully normal mri rule it out entirely???
There's a whole lot of autoimmune encephalitides beyond just anti-NMDA - anti-GAD65, anti-AMPA as mentioned, anti-GABA, etc. I've never seen a presentation of one before, but when I've had anti-NMDA on the differential, usually the others were on there as well. IIRC there's an autoimmune encephalitis panel that's a send out (to Mayo, I think?) that's what we've done when we're considering any sort of encephalitis.

Re: rheum disorders - I don't know for sure, but my brief google seems to support that SLE at the least could present with an encephalitis. I'd defer to the attendings here on the forum for their expertise.

Did the radiologist specifically evaluate the MR for findings seen in CJD? I agree that it's rare and less likely, but that's easy to check. Her symptoms sound fully consistent with an encephalitis of unknown etiology to me, and while CJD is theoretically possible, I think there are more common etiologies you need to look for first.
 
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Medic_90x

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There's a whole lot of autoimmune encephalitides beyond just anti-NMDA - anti-GAD65, anti-AMPA as mentioned, anti-GABA, etc. I've never seen a presentation of one before, but when I've had anti-NMDA on the differential, usually the others were on there as well. IIRC there's an autoimmune encephalitis panel that's a send out (to Mayo, I think?) that's what we've done when we're considering any sort of encephalitis.

Re: rheum disorders - I don't know for sure, but my brief google seems to support that SLE at the least could present with an encephalitis. I'd defer to the attendings here on the forum for their expertise.

Did the radiologist specifically evaluate the MR for findings seen in CJD? I agree that it's rare and less likely, but that's easy to check. Her symptoms sound fully consistent with an encephalitis of unknown etiology to me, and while CJD is theoretically possible, I think there are more common etiologies you need to look for first.
Could you have a false positive though? Our order set has a warning for that if they dont have other symptoms supporting those.

And not sure but the neuro also looked at it and said it looks very normal.
 

differentiating

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Could you have a false positive though? Our order set has a warning for that if they dont have other symptoms supporting those.

And not sure but the neuro also looked at it and said it looks very normal.
I mean, you can definitely have other autoantibody levels high at the same time - I've seen +GAD65 in anti-NMDA and also in mito diseases. But you do have symptoms supporting the investigation, given the patient's clinical presentation of encephalopathy/encephalitis. I'm not sure you really need much more supporting evidence to have it on the differential, just in my (admittedly limited) experience.
 

jdh71

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LP (s far!) showing somewhat elevated protein and glucose. opening pressure was on the low side. Otherwise normal with lyme/hsv/ndma/west nile pending.
Do you have any data on specific ENAs, dsDNA, the MPO and PR3?

I’m inclined to drop the steroid hammer on this patient but those labs need to be cooking somewhere.