To tPA or not to tPA

[Phantom Spike]

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Here's a clinical conundrum. Our hospital has a "frequent flier", a 35 year old woman who comes in almost every month with stereotypical episodes of right arm and leg weakness that last a few hours. She has a history of migraines, and sometimes these spells are associated with headaches, but often they are not. She's had a complete workup (echos, carotid dopplers, MRIs and MRAs of the head) several times, always negative, and is on various combinations of antiplatelets at various times. The general consensus is that these spells are either complicated migraines or conversion episodes, but of course, her chart says "recurrent TIAs" everywhere .

The problem is this: every time she comes in, she is considered "a tPA candidate". Often the ER physician and even the consulting neurologist, if one is called, is unaware of her numerous prior admissions. There is actually nothing in the "indications and contraindications to t-PA" that would preclude her getting tPA, since she never really had been diagnosed with strokes, and recent TIAs are not contraindications in themselves. Would you offer this patient tPA every time she came in? And if not, what argument could you make against it?

 

[bonran]

Doing repeated echos & carotid dopplers every month wont give any new information. Firstly, she is 35yo. One needs to figure out her RF for stroke. If she is low risk & has headaches with some of these events, she may have complex migraines or migraine equivalents (ie like familial hemiplegic migraines). Is there a FHx of migraines in her family? If her symptoms resolve on each of these episodes, then the decision to give TPA will have to be individualized at each visit based on how soon the symptoms resolve & other elements of the Hx as mentioned. One can also use imaging modalities like CT perfusion & correlate it to the NIH stroke scale & symptoms at each visit to supplement the complaints.
Does this patient qualify for prophylactic migraine therapy so that she doesnt come to the ER often?
One must keep in mind the following differentials when dealing with her-migraines, migraine equivalents (w/o headaches), CNS angiitis or peripheral vasculitis with CNS manifestations, seizures & RCVS (Call's syndrome).
I think more history is needed here, how has she been treated & information about labs-inflammatory work up, LP, EEG or cerebral angiogram, that have been done so far.

 

[Phantom Spike]

She had a hypercoagulability workup that was negative, except for being heterozygous for the MTHFR gene. Negative ANA and esr. Negative CT angiogram of the head. Multiple negative prior CTs of the head with contrast (gets one every month!). Negative EEG. Has been advised to try Topamax for headache/seizure prevention, but doesn't take it regularly, so its efficacy is unclear. Depakote was offered, but she doesn't want to take it due to weight-gain concerns. Does have a history of bipolar disorder with major depressive disorder/suicidal ideation, and is on Seroquel and Cymbalta (which would have some headache prevention properties, I would think). No significant family history of migraines or premature cardiovascular disease. Has not had an LP that I know of. In the past, she had been on anticoagulation for DVTs, and continued to have these spells with therapeutic and supratherapeutic INRs. She actually has a pacemaker in for "sick sinus syndrome" so MRIs are out.

 

[HarveyCushing]

Is the patient on OCs by any chance?

 

[neurologist]

Often the ER physician and even the consulting neurologist, if one is called, is unaware of her numerous prior admissions.

This is the heart of the problem right here. Is there no electronic record that can be perused when she comes in so that whoever is on the case can see this history and make a more informed decision?

 

[Phantom Spike]

This is the heart of the problem right here. Is there no electronic record that can be perused when she comes in so that whoever is on the case can see this history and make a more informed decision?

There is, but here's the ER's take, "We have to look at each presentation in isolation. Even if she's been here multiple times for the same thing and all prior workups have been negative, how can we be sure that this time it isn't a stroke, and how can we not offer tPA when there's no contraindication?" This, actually, is the conundrum I was speaking of in my original post.

 

[kutastha]

I think more history is needed here, how has she been treated & information about labs-inflammatory work up, LP, EEG or cerebral angiogram, that have been done so far.

And how about a neuro exam? Does she even have genuine weakness? What's her typical NIHSS score on arrival? If it's just right arm and leg weakness, that would give her a four to six?

I heard nothing about aphasia nor other cortical signs, so it appears to be subcortical. Plus, its the same every time, so unlikely carotids or cardiac in nature. Thus, MRA would be the typical study, but in this patient with a pacemaker, that's not an option. Maybe cerebral angiogram would satisify everyone.

 

[Phantom Spike]

And how about a neuro exam? Does she even have genuine weakness? What's her typical NIHSS score on arrival? If it's just right arm and leg weakness, that would give her a four to six?

I heard nothing about aphasia nor other cortical signs, so it appears to be subcortical. Plus, its the same every time, so unlikely carotids or cardiac in nature. Thus, MRA would be the typical study, but in this patient with a pacemaker, that's not an option. Maybe cerebral angiogram would satisify everyone.

No aphasia. No gaze deviation. Yes, the symptoms are stereotyped, the same every time. The weakness has at times been described as having some components of give-away, but that's a determination that varies from examiner to examiner. In general, strength is rated as 3-4/5 in the upper and lower extremity, with an NIHSS of probably 4-6 on arrival. I doubt we'd be able to get a cerebral angiogram while trying to make a tPA decision. You could get a CT angiogram of the head and neck, but absence of a filling defect is not, as far as I know, a reason in itself to withhold tPA (or is it)?.

 

[AznTrojan]

you could always add a stat CT perfusion scan when you're doing the stat CT brain for a possible TPA candidate..

 

[Strokeguy]

This patient has received IV TPA several times for these symptoms. It is important to have prior records available before you considering 'not giving TPA'. Also do a CT perfusion immediately and then build a case for not giving IV TPA. It would be difficult to withhold thrombolytic therapy unless there is written documentation available that provides evidence of her prior presentation. Do not rely on CTA alone for not giving IV TPA. CTA will only help you making decisions for endovascular therapy. You can never exclude patients from receiving IV TPA if there is no occlusion on CTA - reason is sometimes the clot gets broken and goes must distally and this patient can still benefit from IV TPA.
Also if she presents with large deficits on the NIHSS, then it could be worthwhile doing just an MRI-DWI (takes barely 10-15 min) and if you see no lesion (with prior records available), then you could again build a case for not proceeding with thrombolysis.
Just a word of caution - if no cortical deficits on exam, but she still has weakness, you may not sometimes have a positive DWI acutely (you really need documentation of prior visits).
Another important point to remember - I have seen clots on CTA that were dissolved with IV TPA and subsequent DWI was negative even though there was a prolonged MTT on perfusion MRI (related to existing carotid stenosis). Also DWI can be negative if you are able to achieve recanalization in the first 1-2 hrs.
So in summary - there must be prior documentation available + normal CTP or DWI with some nuances as above.

 

[typhoonegator]

Do you think that maybe you could involve the patient in her own care? That way, on her 35th presentation, she could say, "Hey, I'm weak on one side, but you know, I've been here 35 times in the past with the exact same weakness, and it always gets better on its own". Does she want the tPA?

I'm not sure the CT-P is really going to push you one way or the other. You said there were no cortical signs, so just as strokeguy correctly stated that a normal CTA shouldn't dissuade you from IV-tPA, a small capsular event that causes dense weakness might not give you a demonstrable/dramatic CT-P abnormality. I agree that a quick DWI could be helpful, but the OP already stated that this lady has a PPM, so that's out. As an aside, though, we routinely get the DWI after CT-P in our patients as part of the pre-intervention evaluation, and it is often quite helpful.

I completely disagree with the ED thinking that "you have to look at each presentation in isolation". I'm sure they don't do that with the back pain patients that come in every 2 days looking for morphine. You should use all the information available to you to make an informed decision. What are the chances that the last 20 times she had a right hemiparesis it was a migraine that got better on its own, and this time, with the exact same presentation, its a stroke? Compare that probability to the chance of a complication with tPA therapy in a young healthy patient. The more times she presents, the closer these numbers will get to eachother.

 

[kutastha]

No aphasia. No gaze deviation. Yes, the symptoms are stereotyped, the same every time. The weakness has at times been described as having some components of give-away, but that's a determination that varies from examiner to examiner. In general, strength is rated as 3-4/5 in the upper and lower extremity, with an NIHSS of probably 4-6 on arrival. I doubt we'd be able to get a cerebral angiogram while trying to make a tPA decision. You could get a CT angiogram of the head and neck, but absence of a filling defect is not, as far as I know, a reason in itself to withhold tPA (or is it)?.

No, but you could get a cerebral angiogram to see what those vessels look like even in the absence of symptoms. If she's throwing clots to the same place multiple times she should play the lottery between episodes. Plus, she's had a negative hypercoag w/u - what are her stroke risk factors?

It'd be tough to convince me to give tPA to a patient with improving weakness and an initial NIHSS score of 4-6 in the absence of aphasia.

Probably just me, but a 35 year old female with multiple ED visits for the same symptoms, an extensive and normal workup and "a history of bipolar disorder with major depressive disorder/suicidal ideation, and is on Seroquel and Cymbalta" pins my BS meter. Does she come in with a teddy bear?

 

[bonran]

No aphasia. No gaze deviation. Yes, the symptoms are stereotyped, the same every time. The weakness has at times been described as having some components of give-away, but that's a determination that varies from examiner to examiner. In general, strength is rated as 3-4/5 in the upper and lower extremity, with an NIHSS of probably 4-6 on arrival. I doubt we'd be able to get a cerebral angiogram while trying to make a tPA decision. You could get a CT angiogram of the head and neck, but absence of a filling defect is not, as far as I know, a reason in itself to withhold tPA (or is it)?.

Well you havent told us how long does it take for the weakness to resolve. Is she better the next day or in 48hrs? If she is then you need to think beyond stroke, instead of thinking in a textbook fashion: weakness=stroke=tPA. Since she is a frequent flier, I am assuming she gets alright & goes home without any residual deficits. Have you ruled out the other things listed on the differential? Have you ruled out cocaine? Have you thought of psychogenic strokes ie conversion disorder? Is there a secondary gain or history of physical/sexual abuse in the past? Is she a malingerer (taboo word in the US)?
A little surprising that you cant get an angiogram while deciding about tPA! Is your place a Comprehensive Stroke Center or a Primary Stroke Center? Is there an interventionalist on call for acute strokes?

 

[Phantom Spike]

Well you havent told us how long does it take for the weakness to resolve. Is she better the next day or in 48hrs? If she is then you need to think beyond stroke, instead of thinking in a textbook fashion: weakness=stroke=tPA. Since she is a frequent flier, I am assuming she gets alright & goes home without any residual deficits. Have you ruled out the other things listed on the differential? Have you ruled out cocaine? Have you thought of psychogenic strokes ie conversion disorder? Is there a secondary gain or history of physical/sexual abuse in the past? Is she a malingerer (taboo word in the US)?
A little surprising that you cant get an angiogram while deciding about tPA! Is your place a Comprehensive Stroke Center or a Primary Stroke Center? Is there an interventionalist on call for acute strokes?

I never said I was convinced she was having strokes. I clearly mentioned migraines and conversion disorder as being the leading differentials in my very first post on this thread. If you read between the lines of my posts, you'll see that I don't really believe she is a tPA candidate, but we're often faced with the dilemma of a young woman, with no contraindications to tPA, with right sided weakness, who has come in within the time window. Yes, her deficits always completely resolve, but not for several hours, by which time you need to have made a decision on tPA. My original question was, when a patient presents with this kind of history (recurrent stereotyped episodes), are you or are you not going to offer the patient tPA, and if not, what contraindication will you cite? In a sense, it's a medicolegal question. As for the angiogram, you mentioned a conventional angiogram. I think it would be difficult to arrange that with sometimes an hour's notice, or less, and in the case of an acute stroke, I don't see how it would be superior to a CT angiogram (which has already been discussed in previous posts on this thread).

Just to clarify, the point of this thread is not to ask how you would work this patient up once she's admitted, but what you're going to tell the patient and the ED when she comes in (even if it's for the umpteenth time) with right sided weakness and are asked about tPA.

 

[kutastha]

Just to clarify, the point of this thread is not to ask how you would work this patient up once she's admitted, but what you're going to tell the patient and the ED when she comes in (even if it's for the umpteeth time) with right sided weakness and are asked about tPA.

My note would end with the following: "The patient is not a candidate for tPA due to low NIHSS score and improving symptoms".

tPA would not enter the discussion no matter how many times she came in.

 

[Phantom Spike]

My note would end with the following: "The patient is not a candidate for tPA due to low NIHSS score and improving symptoms".

tPA would not enter the discussion no matter how many times she came in.

But her symptoms generally don't improve until well after the time window has passed. And how low is too low an NIH stroke scale?

 

[kutastha]

But her symptoms generally don't improve until well after the time window has passed. And how low is too low an NIH stroke scale?

You said "stereotypical episodes of right arm and leg weakness that last a few hours". It would strike me as even more odd if they spontaneously resolved. I inferred that they'd be gradually improving.

Our institution uses a soft range of 8-24 as a window, though depending on the case, we may go lower than that. Four to six is pretty low for me - especially in someone whose symptoms resemble a subcortical stroke, and may not be genuine at all.

 

[bonran]

Like I said before, this is not a stroke. She has resolving deficits. MRI is not possible because of a pacemaker so DWIs are out of question. She has multiple admissions with the same presentation resolving in hours. Most likely not a large vessel stroke which would benefit from IA or IV/IA combinations. CT perfusion in an acute setting would help you resolve the question of hypoperfusion (it is not perfect but if one knows how to interpret with CBF, CBV & TTP observations it can be helpful in embolic stroke). CT angiogram would be helpful in ruling out any vasospastic or any obvious vasculitic problems (low sensitivity). Also the fact that these episodes are resolving in hrs, you have to make the case for conversion disorder by ruling out at least once all other possibilities. Which is why PMHx of migraines, Fhx etc are important. She needs an LP with viral, fungal & TB Cx to build a case for or against inflammatory conditions or chronic infections (TB, syphilis, viral & fungal) which can present like this. Combined with angiogram, MRI & LP the sensitivity of diagnosing CNS angiitis or secondary angiitis will go up to 80-90%. She needs a TEE to r/o valve infections & LA myxomas which will r/o cardioembolic reasons for recurrent deficits. Once you have ruled out these major causes, you can make a case for conversion disorder/malingering (frankly, I dont know how to tell the difference between the 2, apparently psychiatrists can-I have never seen them call anyone a malingerer in this country).

Please dont get caught in the "Specialization bias" of calling these events a stroke. These are obviously not strokes. Think beyond & work it out. That is why a neurologist is required (by JACHO guidelines) to run an Acute Stroke, because you have the CLINICAL EXPERIENCE to recognize a stroke & its mimics. ER physicians alone cannot make the decision for giving tPA, though this happens in many hospitals.

There have been many occasions in my fellowship & residency where I have seen cases like this in BATs & we have sent them to psych from ER after an MRI-DWI is negative (granted there are DWI negative strokes but not w/o risk factors) & RF for stroke are minimal. Most residents recognize the few conversion strokes/pseudoseizures/pseudo myasthenia gravis patients who frequent our ER. We intervene to prevent any major work up in our ER on these patients to prevent feeding into the borderline personalities of these patients. Of course we give the benefit of the doubt to some cases where emergency treatment may benefit the patients & try to give them one high yield test (ie MRI-DWI panel) to make sure they are not denied treatment for a genuine stroke. But if negative, these identified patients are promptly shipped to psych/home either from the ER or next morning.

EXAMPLE: We have one pseudo-myasthenic anesthetic tech who would come in for getting INTUBATED!! (actually demanded intubation in ER every few months). He had an extensive work up which was all negative including anti-Ach, anti-MUSK, CT chest with contrast, EMG, single-fiber EMG etc; all negative. We then started identifying him & started getting down to ER in time to prevent intubation by the ER physicians. Surprise of surprises, his male partner who was another healther care professional & would sit next to the bed on each admission taking notes finally realized that the guy is not dead the next morning if not intubated. He lived throught the next 2 visits to our hospital without getting intubated & has not showed up in the last 1 year. His partner stopped taking notes & started believeing the physicians that the guys doesnt have myasthenia. Our EMG department head (nationally recognized guy who started the first EMG program in the US) had to walk upto him on one admission & tell him that in his 30 yr carees he had seen 300 cases of all types of MG, but not one like him. He had 15 admissions in my PGY2 & mid-PGY3 years with 2-3 week stays & million dollar work ups. After 4-5 interventions (multiple demands on the 2 admissions) of successful preventions of intubations he realized he wasnt going to get the attention he craved for in our place & would go home next morning. So, now he doesnt show up & thats less pain for the neurology residents & attendings. QED: once malingerers are caught, they hop to another hospital (I like the UK term: Hospital Hoppers). They are looking for weak physicians with poor history & examination skills & bad clinical decision makers. Thats how they can milk the system.

Or you can be conservative & keep getting million dollar w/os each time she gets to the ER. That will ensure that none of the current generation have any healthcare benefits when we are in our 80s.

The gist is that if she keeps showing up with these episodes in the future with a pacemaker, she needs a prompt CT+ CTperfusion & if negative, needs to get a psych consult (based on clinical judgement & RF analysis-it may not be true if she becomes a heavy smoker or starts using cocaine or 40 yrs down the road when she has had 3 MIs). She needs to have all rare causes of these symptoms ruled out once, her behaviour needs to be documented & the ER physicians need to be made aware of it. She then needs to be called to the O/P clinics in neuro & psych & repeatedly reassured that what she has is non-neurological. SHE NEEDS REASSURANCE!!!!!

 

[typhoonegator]

Nice post, Bonran.

I agree, you have to put the time in and rule out anything else that could be treatable, then you can justifiably manage this patient conservatively from that point forward. If people keep treating her as a stroke patient every time she presents with the same symptoms, eventually she is going to get hurt. First, do no harm.

 

[neuroir]

Not to repeat anyone, but we used to arrange for a prompt neuropsych testing for such patients. If an underlying anxiety/mood/factitious disorder is suspected (and documented) as a cause for nonorganic motor deficits, she can be sent for cognitive-behavioral therapy and that may calm down your ER docs as far as TPA and calling a neurology consult each and every time.

 

[bonran]

You said "stereotypical episodes of right arm and leg weakness that last a few hours". It would strike me as even more odd if they spontaneously resolved. I inferred that they'd be gradually improving.

Our institution uses a soft range of 8-24 as a window, though depending on the case, we may go lower than that. Four to six is pretty low for me - especially in someone whose symptoms resemble a subcortical stroke, and may not be genuine at all.

The decision to tPA is not based on NIHSS alone. One has to think of the pathophysiology behind the stroke, the areas that have been hit (??eloquent areas-speech & vision or brainstem) & the deficits that will be produced.

NIHSS is a crude scale usually for non-neurologists to understand the stroke syndrome. It is notorious for underscoring non-dominant lobe lesions & VB/PCA strokes (because it doesnt take into account the functions of the non-dominant lobe-amusia/prosopagnosia/prosody etc). If you pay attention to the stroked out tissue volumes between RMCA & LMCA strokes you will notice that RMCA will score lower for similar sized strokes-points are given for aphasia in LMCA strokes but nothing similar is scored in RMCA strokes. Similarly in basilar & cerebellar strokes there are no points for vertical gaze restrictions, nausea/vomiting,vertigo, pupils, swallowing etc. The only thing scored (correct me if I am wrong) is horizontal gaze, facial droop, hemianopsias & ataxia. The points system for these is 0-2 or 0-3 unlike limb weakness which scores from 0-4.

We have treated some strokes at our place with NIHSS of 1-3 specially if vision or speech is involved because the deficits from these can be catastrophic. Then there is the question of stroke in evolution, what if the patient with these deficits becomes worse 5 hrs down the line without treatment because their presenting NIHSS was low? One will have missed the tPA window by all current criteria & unproven therapies like mechanical interventions will have to be employed late into the event with questionable outcomes. However, the same arguement cannot be made for plain sensory strokes or those that are rapidly improving.

There is more to strokes than just NIHSS & tPA. One has to think through it.

 

[kutastha]

The decision to tPA is not based on NIHSS alone. One has to think of the pathophysiology behind the stroke, the areas that have been hit (??eloquent areas-speech & vision or brainstem) & the deficits that will be produced.
[...]

There is more to strokes than just NIHSS & tPA. One has to think through it.

As I alluded to in my previous post #21-

>>It'd be tough to convince me to give tPA to a patient with improving weakness and an initial NIHSS score of 4-6 in the absence of aphasia<<

 

[Wheezy]

As I alluded to in my previous post #21-

>>It'd be tough to convince me to give tPA to a patient with improving weakness and an initial NIHSS score of 4-6 in the absence of aphasia<<

It can be a tough call but here are a couple of points:

1. This patient: seems like since complicated migraine vs. conversion are the top 2 in the differential. The team needs to decide which it is & talk to the patient. if it's migraine then try prophylaxis at adequate dosages for an adequate time and if it fails, try another drug. If it's conversion, try CBT & address comorbidities.

2. Generally, i.e. in other patients, improving weakness or low NIHSS or absence of aphasia shouldn't deter the physician from giving tPA. Because:

a. Low NIHSS patients still benefit from tPA. See subgroup analysis of NINDs trial. Generalized Efficacy of t-PA for Acute Stroke Stroke. 1997;28:2119-2125.

b. absence of aphasia occurs in lacunar strokes (internal capsule, midbrain, pons, medulla)

c. In patients with improving symptoms withholding tPA leads to bad outcomes:

“Of those patients presenting within 3 hours, 27% received the therapy but a further 31% were excluded because their symptoms were either considered too mild or were rapidly improving. Subsequently, a third of these patients were left either dependent or dead, bringing into question the initial decision not to treat” Barber et al. Why are stroke patients excluded from TPA therapy?. Neurology 2001;56:1015-1020

I'm not encouraging reckless use of tPA but a lot of reasons for withholding it, don't hold up!

 

[Strokeguy]

It can be a tough call but here are a couple of points:

1. This patient: seems like since complicated migraine vs. conversion are the top 2 in the differential. The team needs to decide which it is & talk to the patient. if it's migraine then try prophylaxis at adequate dosages for an adequate time and if it fails, try another drug. If it's conversion, try CBT & address comorbidities.

2. Generally, i.e. in other patients, improving weakness or low NIHSS or absence of aphasia shouldn't deter the physician from giving tPA. Because:

a. Low NIHSS patients still benefit from tPA. See subgroup analysis of NINDs trial. Generalized Efficacy of t-PA for Acute Stroke Stroke. 1997;28:2119-2125.

b. absence of aphasia occurs in lacunar strokes (internal capsule, midbrain, pons, medulla)

c. In patients with improving symptoms withholding tPA leads to bad outcomes:

“Of those patients presenting within 3 hours, 27% received the therapy but a further 31% were excluded because their symptoms were either considered too mild or were rapidly improving. Subsequently, a third of these patients were left either dependent or dead, bringing into question the initial decision not to treat” Barber et al. Why are stroke patients excluded from TPA therapy?. Neurology 2001;56:1015-1020

I'm not encouraging reckless use of tPA but a lot of reasons for withholding it, don't hold up!

---------------------
Agree with above.

 

[TopSecret]

The 35 year-old patient has strokelike episodes and a cardiac conduction block requiring a pacemaker?

Maybe she has mitochondrial disease. It'd be worth looking into.

 

[aaddnl]

It can be a tough call but here are a couple of points:

1. This patient: seems like since complicated migraine vs. conversion are the top 2 in the differential. The team needs to decide which it is & talk to the patient. if it's migraine then try prophylaxis at adequate dosages for an adequate time and if it fails, try another drug. If it's conversion, try CBT & address comorbidities.

2. Generally, i.e. in other patients, improving weakness or low NIHSS or absence of aphasia shouldn't deter the physician from giving tPA. Because:

a. Low NIHSS patients still benefit from tPA. See subgroup analysis of NINDs trial. Generalized Efficacy of t-PA for Acute Stroke Stroke. 1997;28:2119-2125.

b. absence of aphasia occurs in lacunar strokes (internal capsule, midbrain, pons, medulla)

c. In patients with improving symptoms withholding tPA leads to bad outcomes:

“Of those patients presenting within 3 hours, 27% received the therapy but a further 31% were excluded because their symptoms were either considered too mild or were rapidly improving. Subsequently, a third of these patients were left either dependent or dead, bringing into question the initial decision not to treat” Barber et al. Why are stroke patients excluded from TPA therapy?. Neurology 2001;56:1015-1020

I'm not encouraging reckless use of tPA but a lot of reasons for withholding it, don't hold up!

I dont know where to start here. This case is very typical of physicians not being able to make pragmatic obvious decisions. The suggestions that this patient should receive TPA or get more testing done is representative of the overutilization and overtreatment that doctors (including neurologists) are trained to do, just throwing away any and all common sense.
There is NO WAY someone should give this woman TPA. Stroke is your third most likely diagnosis, and even if it were a stroke (which it is not), giving tPA to a patient like this IS completely reckless.
Any reasonable stroke specialist or general neurologist can tell you that treating patients w/ TPA who have improving deficits, subcortical deficits (that will get better with no treatment), and in general low NIHSS is playing with fire and generally very dangerous and subjecting a patient who will recover from her stroke to untoward risk.
Despite the claims about the subgroup analysis from the NINDS trial, IV tPA is not a home run even for patients appropriately selected (look at ECASS-3), and you can't use subgroup and secondary analysis to justify management like that. You dont see that in other trials and no RCT on pts with low NIHSS would show a significant benefit for tPA, which is why it would not be performed. They would probably stop the trial due to higher mortality from ICH in tpa group. You only get the mortality and functional benefit from TPA when you give it to the correct patient--someone with a significant stroke (usually cortical and NIHSS>8 or so) and preferably as early as possible. The argument about bad outcomes in patients who were excluded from the trial is fraught with errors because you dont know anything about their clinical background and this is just a random snapshot of patients and basically just the speculation of someone trying to justify more widespread tPA use b/c they have vested interest in it. It is much more difficult in this day and age for clinicians to make a stand and decide not to subject patients to dangerous treatments that they dont stand to benefit from and unneccessary procedures. One must be able to diagnose a patient clinically and trust their knowledge of the disease process and the course of the disease.
The suggestion that, "the stroke could worsen in the next few hours, so tPA should be given," could be used to justify giving tPA to anyone with an NIHSS of 1.
Doing a CT-P, MRI or angiography is also completely ridiculous in this patient who has had these tests done every one of the 15 times she comes in with the same sx from her conversion d/o or "complicated" migraine.

 

[Strokeguy]

I agree that clinical 'pragmatism' should be used in this specific patients to preclude IV TPA, given the established pattern of presentation and prior evaluations.
But excluding patients with low NIHSS scores from IV TPA is also a mistake. NIHSS is not meant to be used as a criteria for thrombolysis. Patients with homonymous hemianopsia, hemiplegia or aphasia alone have significant deficits (but low NIHSS), that benefit from thrombolysis. The NINDS trial clearly showed that even though mortality is not significantly influenced with IV TPA, the functional outcome is better even in pts with NIHSS 2-8.
NOTE- These pts in the NINDS had low scores but significant deficits. A pt with left homonymous hemianopsia + left hemiparesis could well have NIHSS <8 - Would you not treat ???
A pt with NIHSS >8 is very likely to have a large artery occlusion - recanalization rates with IV TPA is about 35 %. You can argue that endovasc therapy is not standard of care, but still an important consideration.
But reserving IV TPA for NIHSS>8 alone is a disaster and invitation for medical malpractice, given the significant evidence that has now accumulated in favor of IV TPA.
I do agree about the associated risks of ICH - Look at the accumulated evidence - the risk of post-thrombolytic ICH is more with the size and severity of the infarct.
No stroke expert with any reasonable experience would reserve IV TPA for NIHSS>8 alone.

 

[bonran]

I am writing this as I make the decision. Just got a call asking about this 90yo demented female at a nearby hospital who was about to be discharged home when the family medicine resident noticed her having "some" difficulty with speech and "some" left grip weakness. Last seen normal 30 minutes back. She is not oriented to place or person due to her baseline dementia. Now, she does have a low "NIHSS" of 2-3, 1 for mild aphasia, 1 for mild dysarthria & ? for weakness. To the proponents of low NIHSS thrombolysis, should I t-PA her? Or is this all just her dementia (?semantic), maybe worsened by metabolic or infectious complications?
I ain't t-PAing something that isnt even a well defined stroke syndrome.

 

[aaddnl]

I hope you are joking about giving that lady tPA. that would be insane. this is exactly the point i was trying to make about when you start giving tPA to people with low NIHSS, you end up treating a bunch of stuff that probably isnt stroke. a guy at an outside hospital here just got tPA for conversion disorder last week and had a serious GI bleed. the real question is, what benefit does the patient stand to gain? too often in medicine doctors treat patients to make themselves feel better. what kind of improvement in quality of life will the 90 y/o demented lady with mild deficits really get with this treatment? and does she even have stroke? probably not, sounds like an encephalopathy and the "grip weakness" that the family medicine resident reports sounds fishy and mild at best. and it sounds like the points you are giving her for her NIHSS are her baseline dementia. i would be skeptical about stroke in this patient, particularly based on the Family practice doc's exam, but the point is, even if she had a stroke, there's no way you can justify giving that patient tPA (though i'm sure you could find plenty of misguided people who would).

 

[aaddnl]

\
No stroke expert with any reasonable experience would reserve IV TPA for NIHSS>8 alone.

This is flat-out not true. The two most respected national stroke experts where i did residency reserve IV TPA for NIHSS equal to or greater than 8 (with rare exceptions) and they have credentials to match anyone in the "stroke community."

 

[bonran]

Of course I was joking. This 90yo lady didnt turn out to have anything on MR.

So last night there was this lady comes into an ER 2hrs away by road, who has aphasia followed by some improvement in speech & "minimal weakness" (per the ER doc on phone) in her left arm. He had no NIHSS, no PMHx for me & expects me to decide on tPA over the phone. CT is negative & she is at 2hrs from witnessed onset. I ask him to dig into the PHx & the lady has had encephalitis 3 yrs back. I didnt give her t-PA & asked him to fly the pt into our ER to get an MR. Weather being bad she is prepped for a road transfer. Family decides to wait for the weather to clear & the doc gets back to me about this. I ask him to get an MRI if the patient will be in his ER for another few hrs to see if there is an underlying "stroke" (are you kidding me-this is a nonconvulsive seizure coming from her left temporal lobe- the region of her prior, likely HSV encephalitis). I get paged at night about the MRI negative for stroke.

I am sitting on another "stroke" called in ER right now. Pt at 3 hrs arrived with a "facial droop & dysarthria". Walking into the ER I see an overtly psychotic patient with severe tardive dyskinesias with what looks like a mild left droop (through her orofacial dyskinesis). She is flailing her arms all over & is speaking clearly but inappropriate in her response. Now she may have a posterior parietal stroke with Wernicke's aphasia & some facial droop. She qualifies for ECASS III criteria for thrombolysis with NIHSS of 3-5. I would normally thrombolyse someone with a distinct aphasia with a low NIHSS, but with her brief reactive psychosis & her tardive dyskinesis, I want to wait for the CT-perf/MR before I decide that. I might still miss a small cortical embolic stroke on CT perf, but not a large vessel thrombus who would deserve t-PA & then moving to the angio-room. However this lady might need a cogentin drip more than a t-PA dose.
I think people need to make decisions based on clinical presentation rather than blindly t-PAing everyone who walks in with low-NIHSS & minor/questionable neurological findings.

 

[AlternateSome1]

(with rare exceptions)

So you are arguing and stating that the previous poster is correct?

 

[aaddnl]

No, you missed the point there Charlottesville, the previous poster is saying nobody reserves tpa for people w/ nihss 8 or above and i'm saying that's not true i know excellent stroke neurologists who do. i said rare exceptions b/c i may have seen them treat someone w/ a NIHSS of 7 once in a very unique situation(there are always rare exceptions), but in general they reserve tpa for higher NIHSS. the previous poster said nobody in the stroke community does this and thats not true.
Bonran, i understand you were joking, but why would you get an MRI on the 90 year old? or the CT-P on the pt w/ psychosis? seems a bit much, i think those decisions could be made with a good history and physical.

 

[typhoonegator]

You have an interesting interpretation of the literature. I completely agree with the prior post by strokeguy. Why make a cutoff of 8? Why not 9? 7? The NIHSS is not a great tool for such an evaluation, and you'd be placing a lot of faith in it if you wanted to go against national guidelines and prior literature to make your treatment decisions.

Patients can have very significant and localizable deficits with an NIHSS lower than 8. Lacunar syndromes do seem to benefit from tPA, possibly artifactually, but possibly not. There isn't sufficient equipoise for another evaluation, so the point is rather moot.

But then again, I'm just a neurocritical care fellow, I should probably get back to managing ICPs or something.

 

[Strokeguy]

Clinical equipoise and not NIHSS alone should be used when deciding thrombolysis. Again using NIHSS >8 as a criteria for IV TPA is ridiculous. I am very curious about who those 'national stroke experts' are that use this criteria.
I have been fellowship trained by 'national stroke experts' that have designed and conducted landmark stroke trials. I don't even have to mention which these trials are. I have also shared data as a part of SPOTRIAS with the NINDS in this regard, interacted with several other stroke experts at the AAN and ISC (International stroke conferences). Frankly, I am surprised, even shocked if any real stroke experts ever used NIHSS > 8 as a cutoff for IV TPA. It is even more surprising now, when we have NIHSS = 6 as a cutoff for MRRESCUE and 10 for IMS-III.
Anyone with decent neurologic skills can differentiate psychotic symptoms or elderly pt with UTI and confusion with frank aphasia that must be treated. I have seen a few cases during fellowship - seen clots in the distal M2, and these are the pts that do well with IV TPA alone.

 

[bonran]

I dont agree with arbitrary cutoffs for thrombolysis, as I have said in my previous post. Decisions should be made on clinical presentation, scope of recovery, what will recover, imaging evidence, etiology along with NIHSS. Sometimes it is not possible to have or to do all these. Besides all clots are not equal, Strokeguy; just as all strokes are not equal. A fresh platelet plug will dissolve with thrombolysis if it is done early enough, regardless of where it is. I have seen them break at 2.45h with iv tpa alone in a few patients just last week in the M1 stem. Then there are those on whom tpa has no effect. Clot physiology surely has something to do with it, something that has not been looked into extensively. An organised clot coming from the LA or L auricle is not the same as a recent platelet plug formed on a fractured plaque.

Clinical equipoise is a big word but cannot be practiced at bedside on an individual patient. It is used by "experts" for reaching a consensus for developing guidelines for practice or clinical studies on variables for which there is no evidence. Here is the definition:

The principle of equipoise, provides the ethical basis for medical research involving patients assigned to different treatment arms of a clinical trial. Clinical equipoise means that there is genuine uncertainty over whether or not the treatment will be beneficial. Even if the researcher truly believes in a hypothesis, there is no actual proof that the benefit exists. Once there is sufficient evidence the research is usually stopped since clinical equipoise is not met.

Patients cannot be treated on hypotheses or expert consensus alone. Other physicians may have their own equipoise & may not agree with "expert opinion". Besides, clinical equipoise has to take into account patient equipoise who may refuse a particular treatment including tPA.

Just some feedback, the schizophrenic patient indeed did have a left M2 posterior (parietal) embolic looking stroke. We could get a very shaky MRI 3 days after her stroke. Her dyskinesias improved with klonapin & she was able to speak more. Her residual dysphasia is moderate. She will stop the anticoagulation we put her on, once she goes back to the community as she has to pay for her cocaine.

It is not easy to discern what is stroke & what is not even with "decent neurological skills". I too have trained with top of the line Stroke Physicians involved in frontline stroke trials & in a high volume stroke fellowship. I have also trained with some renouned nerologists, epileptologists, neuromuscular specialists, neuroophthalmologists, neurointerventionalists & neuroradiologists helping me think beyond stroke & not developing a specialization bias. Having seen the clinical skills of residents in the program where I did my fellowship, my home residency training was far superior in doing & documenting a clinical exam. Regardless, the bedside exam has its own limits & physical signs have their own sensitivity & specificity in an acute situation.

As far as cutoffs for studies are concerned, they are designed to garner large vessel strokes with a higher sensitivity in multiple centers across the globe where practices might not be as standardized as a comprehensive stroke center. Theses cutoffs are randomly decided based on personal experience around coffee tables & barstools. They should not be implimented in clincal practice without thinking through the etiology.

 

[Strokeguy]

Combining clinical skills and neuroimaging with therapy is how you should treat strokes. Your M1 case is not unusual and not surprising at all. That pt is one among those 30% with M1s that recanalyze with IV TPA. This is where TCD is useful non-invasive tool.
Even clot composition has been studied though not pathologically. There is only one article in 'Annals of Neurology' that looks at clots after mechanical retrieval. The biggest drawback in this approach - when you use IA lysis or clot extraction you distort and fragment the clot so much, that any path analysis is meaningless.
There is no way to say whether clots in the heart from AFib are old or new. Even assuming clots in the heart as organized/hard is erroneus when you do not know when the clot started forming.
RBC rich clots (imaging correlates) thrombolyze well with IV TPA compared to platelet rich clots. This has been published. But it is difficult to design clinicopath studies.
We still have not reached a stage yet when we can clearly identify a clot that would lyze completely with IV therapy. There is however, just early evidence that 'hyperdense' signs on plain CT are least likely to open with IV tpa.
Regarding 'scope of recovery', it is well known that pts with large strokes (high NIHSS) will in general have a bad prognosis. The only credible indicator of good or decent prognosis from several studies so far is 'recanalization'. You have to open the occluded artery in the shortest possible time and must never open it at later intervals.

''It is not easy to discern what is stroke & what is not even with "decent neurological skills".'' --- This is where you use neuroimaging and clinical sense in situations with patients in confusion/altered sensorium. You cannot use NIHSS cutoffs.

 

[bonran]

I think we are saying the same thing. 😕

 

[typhoonegator]

I was referring to equipoise regarding the issue of whether we could consider having another tPA trial using this arbitrary cutoff of NIHSS 8 to lyse patients. We don't have equipoise on this issue, and so we can't do a new trial.

Honestly, there is nothing in my post which suggests that I am trying to apply the concept of equipoise to individual patient care. I am well aware of the definition of the term, thanks.

We are all saying the same thing at this point (except the person who thinks we should not tPA patients with significant neuro deficits with NIHSS <8), so what is the point of incisive commentary? This thread has run its course.