Question of the Week

For August 13, 2019

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New lacunar strokePostictal weakness after seizure, related to febrile illnessNew embolic strokeRecrudescence of prior stroke symptomsProgressive myopathy

Key Learning Point View Case Presentation

When patients with prior stroke experience recrudescence, the symptoms are usually similar to their initial presentation but not as severe.

Detailed Feedback

Patients who have had neurologic deficits as a result of stroke or multiple sclerosis sometimes experience reemergence or recrudescence of those deficits in the setting of an intercurrent illness. The most common triggers include infection, hypotension, hyponatremia, hypoglycemia, insomnia, stress, and benzodiazepine use. Recrudescence occurs most commonly with middle cerebral-artery infarcts and can lead to language, sensory, and motor deficits. Gaze preference, hemianopsia, and neglect are not typically observed.

Recrudescence is often a diagnosis of exclusion and must be distinguished from a new neurologic event. The symptoms experienced during recrudescence are typically similar to those of the initial presentation but less severe. If symptoms occur that were not present at the time of the initial injury, they should be evaluated as a possible new event.

In this case, the patient has an unknown international normalized ratio and significant risk factors for stroke, including suboptimally controlled blood pressure at the time of the examination. This raises the possibility of a new embolic or lacunar stroke. However, the patient reports adherence to his medications, and his current deficits are similar to but less severe than his initial presentation, they occurred in the setting of illness, and they now seem to be improving — all of which make recrudescence more likely than a new stroke. It would be very unlikely for a new stroke to cause exactly the same symptoms as the first, especially a lacunar stroke, which is a different mechanism from this patient’s first stroke.

Although seizure can occur in the setting of infection and can lead to a Todd paralysis (transient unilateral postictal weakness, often contralateral to the site of seizure onset), this patient has no reports of seizure activity or any other findings, such as incontinence, that might suggest seizure.

The asymmetry of his symptoms and lack of proximal weakness make a new progressive myopathy unlikely, particularly at the age of 82.

Last reviewed Jun 2020.


Topcuoglu MA et al. Recrudescence of deficits after stroke: clinical and imaging phenotype, triggers, and risk factors. JAMA Neurol 2017 Sep 1; 74:1048.   > View Abstract


  1. Mohammed W Omar August 13, 2019 at 9:33 am - Reply

    A very interesting and complex case,but the detailed feedback shed enough light for diagnosis. My question is was any testing done or one can r/0 new stroke for sure,I will not be sure.

  2. John Kiraly August 13, 2019 at 11:15 am - Reply

    Excellent discussion of the differential diagnosis. What tests would you order to confirm your impression?

  3. Pete Cohen August 13, 2019 at 11:21 am - Reply

    Very instructive, but in practice I don’t see how you can be certain that it is not a new event.

  4. MD Muhammed Beeai August 13, 2019 at 11:36 am - Reply

    Very instructive

  5. John Rizos August 13, 2019 at 11:48 am - Reply

    Thank you for, great clinical example that I was not familiar with.

  6. stavroula tomatsidou August 13, 2019 at 11:50 am - Reply

    Thank you !excellent clinical case

  7. alfonso e sierra August 13, 2019 at 12:02 pm - Reply

    The facts that the new symptoms and signs are similar and already these are improving in short time, what is discussed in the feedback from the NEJM are very important in considering the diagnosis of recrudescence, search for biomarkers will find if any, these of acute infection and/or inflammation. Excellent reaching exercise.

  8. John Schmitz August 13, 2019 at 12:15 pm - Reply

    Did they take an INR anyway? While not immediately diagnostic, it seems like a wise precaution and opportunity to assess anticoagulation therapy.

  9. Hafiane August 13, 2019 at 12:21 pm - Reply

    Very interesting case.Do you need to practice a scan or MRI.

  10. M.Ali Afzal August 13, 2019 at 12:27 pm - Reply

    It’s a very common scenario in clinical practice and history and examination mostly gets you the answer!! But as mentioned beware of a new stroke!!

  11. TAREQ BURGAN August 13, 2019 at 12:29 pm - Reply

    Excellent case and feedback.

  12. PRAVEEN YADA August 13, 2019 at 12:35 pm - Reply

    Very interesting observation, but we have to perform a MRI DWI brain to establish that patient does not have a new stroke.

  13. Adan R Atriham August 13, 2019 at 12:38 pm - Reply

    As the expiation say… recrudescence of prior stroke IS a dx of exclusion. In the acute care setting, any one presenting with stroke-like symptoms IS stroke until proven otherwise. I would not dare to call this just an exacerbation of prior stroke without appropriate and timely evaluation with neuro-imaging.

  14. Enrico Motz August 13, 2019 at 12:57 pm - Reply

    Excellent case and feedback, thank you. I understand that type, entity and evolution of symptoms during intercurrent febrile illness are diagnostic. Only, I would like some more explanations / hypotheses on the mechanism of transient recrudescence of prior stroke symptoms

  15. Massoud Alipour August 13, 2019 at 1:04 pm - Reply

    Febrile illness: in this case probably pulmonary, can exacerbate the previous neurologic symptoms in an elderly. Doing aTCD, especially comparing it with the previous studies would be revealing.
    Changes in doppler characteristics of MCA, determining PI & RI: (Pulsatility & resistivity indices ) may be helpful especially if the CNS findings lingers on.
    Probably Brain CT and MRI were not revealing.

  16. Mbi Mbi August 13, 2019 at 2:03 pm - Reply

    I would have never guessed that you for this case. I was convinced it’s lacunar infract.

  17. Lars Leftoofer August 13, 2019 at 3:24 pm - Reply

    Would transcranial doppler followed by serum ESR testing be of benefit?

  18. Sherrod Shiveley August 13, 2019 at 3:33 pm - Reply

    Great case. We see this all the time in hospital medicine. I think this patient meets sepsis criteria with fever and the neurological changes.

  19. A. Sankaranarayanan August 13, 2019 at 3:42 pm - Reply

    Well, a complex case. The feed back was instructive. But how do we confirm that this is not a new event?

  20. Chidambaran August 13, 2019 at 3:43 pm - Reply

    Thank you.

  21. alfonso e sierra August 13, 2019 at 4:19 pm - Reply

    Findings or not of imaging could or not resolve if this is a new Stroke. For its previous history, this patient is prone to have new ones that usually announce themselves with more signs and symptoms, different to the initial one. For anyone interested in reading about the relation of infections and recrudescence a fairly good discussion just appeared in Post-stroke Recrudescence from Infection: an Immunologic Mechanism? Rocha EA 1,2 Topcuoglu MA 3 Singhal AB 4 Transl Stroke Res. 4 2019;10(2):146 summary available in Pubmed.

  22. Jesus Bianco August 13, 2019 at 5:03 pm - Reply

    No cardiologist would diagnose this case the way it was framed. I suspect Dr Atriham is a neurologist.

    On an VKA ….why did this patient neglected the INR?

    This is a question that will not appear in the ABIM Board of Cardiovascular Disease.

    Picky, Picky……..

  23. K Kidoguchi August 13, 2019 at 6:13 pm - Reply

    Excellent case. I have never encountered such a confusing case. NEJM Knowledge+ provides us teachable moment. Thank you.

  24. William Mattey August 13, 2019 at 8:11 pm - Reply

    Thank you for your excellent teaching case. Agree with your comments and above Physician interesting comments.

  25. John Barclay August 13, 2019 at 8:35 pm - Reply

    Still need that INR done right away as noncompliance with INR monitoring can easily lead to under or over anticoagulation, and he is in Atrial Fib.

  26. Missana August 14, 2019 at 3:31 am - Reply

    Great case study, I never come across such a thing as recrudescence that Comes 4 years later… Is it possible???
    This is new to me

  27. Erden Asardag August 14, 2019 at 7:57 am - Reply

    One can’t be sure about the mentioned diagnosis until detailed tests and mrı ct has been performed in real world. This is a perfect question for any exam. Thank you.

  28. Jaime Leonardo Salazar August 14, 2019 at 8:02 am - Reply

    I think recrudescence of prior stroke is an exclusion diagnosis, so I would order an MRI to be sure. For that reason my initial diagnosis would be a new embolic stroke.

  29. Yogish August 14, 2019 at 11:14 am - Reply

    In view of the fever , I. Would also do a blood culture to rule out endocarditis causing embolii

  30. Yogish August 14, 2019 at 11:25 am - Reply

    Would a blood culture be appropriate to rule out embolii from infective endocarditis…???

  31. siraj siddiqui August 14, 2019 at 11:48 am - Reply

    Thanks for nice cases

  32. Mario Lerman August 14, 2019 at 1:19 pm - Reply

    very useful

  33. Ethan Brown August 14, 2019 at 2:00 pm - Reply

    Hi all –

    I am the Neurology Section Editor for NEJM Knowledge+ and wanted to take the opportunity to respond to some great comments. This case is challenging but, as others have mentioned, can be a common occurrence in clinical practice. As the detailed feedback mentions, recrudescence is the most likely cause, though in practice further work up would be appropriate to rule out the less likely differential diagnoses.

    Practices vary and the management is likely specific to the clinical situation. However, based on the details we are given here, the necessary work up includes an MRI of the brain to evaluate for acute stroke and ordering an INR to ensure warfarin is at a therapeutic level. While the symptoms the patient felt are similar to his prior stroke, a stroke in a nearby area could have caused leg weakness or unsteadiness that made him feel similar to his previous symptoms. Furthermore, we do not know if the deficits on his current exam are the same as before, though in practice we may have better documentation. A new acute stroke could change management, such as adjusting the dose of his warfarin (if his INR is not at goal) or transitioning him to a different oral anticoagulant.

    Regarding whether or not this is a septic embolus, again the MRI would rule that possibility out. However septic emboli in this case is unlikely because (a) patients appear much more ill and likely he would not be recovering, and (b) there is no murmur to suggest endocarditis. Blood cultures would therefore not be necessary based on the information provided.

    Thank you for all the great comments,

    Ethan Brown

  34. Mauro Barabani August 14, 2019 at 3:13 pm - Reply

    Agree with Dr. Adan R Atriham. We can not rule out a new ictus, we do not have neither MR imaging nor INR. Why isn’ t he in NOAC?

  35. Tulin isik August 14, 2019 at 6:23 pm - Reply

    WE must have a MR imaging before WE jump ön a conclusion. Anyway a nice case.very insructive as usual.thank you

  36. Tom Vescio August 14, 2019 at 6:25 pm - Reply

    Fever and a new neurologic deficit . . . one would never be wrong to obtain blood cultures to exclude a potentially lethal diagnosis such as infective endocarditis (lack of murmur does not exclude IE diagnosis).

  37. Sheila Damewood Larson August 14, 2019 at 11:37 pm - Reply

    This may be too simplified, however, for me, it makes sense that is recrudescence. How many times when YOU haven’t been feeling well have old aches and pains crept back up on you? Not saying not to run tests to be certain. Time is of the essence with a stroke though, so better safe than sorry.

  38. Witteveen Ron August 15, 2019 at 4:10 am - Reply

    Y’ll need a DWI MRI for this (recrudescence) diagnosis

  39. elias azar August 15, 2019 at 8:46 am - Reply

    excellent case thank you.

  40. MIA August 16, 2019 at 5:07 am - Reply

    Really a practical quiz. Very often we see similar cases giving rise to increasing motor weakness of extremities already involved in previous stroke. I always thought of new stroke in the same territory and recurrence of previous stroke is new to me. I wonder what is the likely cause of recurrence of symptoms during intercurrent illnesses. Thank you NEJM,

  41. Sandip Ghimire August 16, 2019 at 9:55 am - Reply

    Very useful case, thank you!

  42. Dr Gholam reza noori August 17, 2019 at 12:47 pm - Reply

    Thanks it’s wade good case.
    Dr Gholama reza Noori
    Cardiologist and internist.

  43. Mohanned Omar August 17, 2019 at 4:31 pm - Reply

    Thank you Ethan Brown for clarifications.

  44. Muhammad Yousuf FRCPI, FRCPE, FACP August 19, 2019 at 1:03 pm - Reply

    On reading the study quoted in the discussion on this case, authors used the following criteria to diagnose post-stroke recrudescence (PSR): 1. Transient worsening of residual poststroke focal neurologic deficits, or transient recurrence of previous stroke-related focal neurologic deficits 2. Chronic stroke on brain imaging 3. No acute lesion on DWI 4. Symptom duration >1 hour without new DWI lesion; no suspicion for low-flow TIA from cerebral artery stenosis or occlusion 5. No clinical or EEG of seizure around the time of the event.

    At best this diagnosis can be made in centers where imaging (MRI or diffusion imaging CT), EEG, and other ancillary investigations are available and affordable. However, in third-world countries where these facilities are either not available or the patient can not afford the cost of these imaging, my best bet would be:

    1. If the previous stroke deficit worsens by one grade in power, 2. The deficit does not recover with the recovery of the precipitating factor in few days, and 3. The patient did not have any new infection or features of endocarditis or clinical focal epileptic seizures originating from the same side of the brain.

    However, in most of these cases, the treatment will still be the intensification of control of the underlying stroke risk factors, it may not always be possible or even necessary to confirm this diagnosis.

    Why some patient only really had the recrudescence and not all such patients gives us a lesson –

  45. Thomas O. Gore August 19, 2019 at 5:41 pm - Reply

    Appreciate this case and knowledgeable discussion. There is no progression of neurological signs and symptoms; just the opposite. Since CVA often is accompanied by increased body temperature along with patient’s worry about a new stroke, it is wise to get imaging to put the issue to rest.

  46. ThomasO, Gore August 19, 2019 at 6:39 pm - Reply

    Appreciate case and knowledgeable discussion. With patient’s respiratory infection there might be some cerebral hypoxia to explain return of the neurological signs and symptoms. His oxygen saturation level would be affected. He may have some cognitive impairment of executive function given his failure to monitor his INR. I would suggest administering the Mini-Mental Status Exam along with treatment adherence counseling with involvement,if possible of a family member or other care giver.

  47. Muhammad Yousuf FRCPI, FRCPE, FACP August 20, 2019 at 11:06 am - Reply



  48. Emmet Kenney August 20, 2019 at 10:53 pm - Reply

    Someone is excited because they brought not just a zebra, but a unicorn out of the closet. Clinically if this case is not treated as a presumptive recurrent embolic stroke from the moment this patient walks into your office, you are committing malpractice. Ordering an INR and immediate urgent neuroimaging must be done which Dr. Brown himself states. I wonder if Dr. Brown’s imaging department would accept “recrudescence of a prior stroke” as a Medicare approved diagnosis for payment of an MRI? Or would they call the PCP and ask for a different diagnosis because recrudescence is not covered? If you are sure if it is recrudescence, to list stroke as the reason for the study is putting down a false statement in order to trick and insurance company or medicare into paying for a test. This is known as fraud.

    So do we really think as part of a general knowledge/training question the answer is recrudescence? or should the question read “after ruling out a recurrent stroke with an MRI and confirming that the INR is in the therapeutic range, what other diagnoses must be considered?”

  49. Shahpar Bagheri August 21, 2019 at 1:05 pm - Reply

    Thank you.

  50. J. Bailey, MD August 22, 2019 at 1:41 pm - Reply

    That seems unreasonable in view of new onset fever.

  51. Alexandre Mello January 1, 2021 at 4:35 pm - Reply

    Excellent clinical reasoning and differential diagnosis, but in real life, we would all probably order brain imaging to rule out a new stroke.

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