66 year old male with past history of hypertension on regular treatment presented with sudden onset of weakness of left arm and leg with facial deviation and slurring of speech. After ruling out other factors, patient was clinically diagnosed as right MCA infarct. Patient’s NIHSS was scored to be 7. CT brain with CT angiography revealed no bleed but demonstrated focal occlusion of the right main stem MCA. Large arteries extracranially were reported to be normal. Patient presented within the time window and had no contraindication to use of IV actilyse. Patient was administered IV actilyse 70 mg, and monitored. CTA post thrombolysis revealed partial recanalistion of the M1 branch of the right MCA. The mechanism of the stroke was large vessel disease of the intracranial vessels / Non carotid large vessel disease (M1 block). Patient recovered well and the NIHSS on discharge was 0 and MRS was 0. Patient was discharged on antiplatelets and statin ie on best medical therapy.
1 month later patient presented with an episode of left arm weakness and unresponsiveness lasting for 15 minutes. Patient’s symptoms resolved on his own and recovered completely. MRI brain was performed which confirmed a subacute infarct in the right MCA territory.
After another 2 months the patient presented with left hemiparesis and left facial deviation and slurring of speech. NIHSS on admission was 12. CTA brain demonstrated a occlusion of the right MCA once again with – infarcts in right insular cortex and right fronto-parietal white matter, right periventricular white matter. Once again patient presented within the window for treatment of IV actilyse. Patient had already been treated once earlier with IV actilyse, three months prior to this presentation. Patient was once again treated with IV actilyse and monitored. Post thrombolysis MRA brain demonstrated right MCA infarct with no hemorrhagic transformation and partial recanalisation of the M 1 segment of right MCA with sluggish flow. Patient improved remarkably and NIHSS reduced to 5, MRS was 2. Patient was advised to undergo intracranial stenting in view of stroke while on best medical treatment.
Patient was stented in the right MCA, one month later, patient recovered well with complete recovery in the hemiparesis and remarkable improvement in speech. The current NIHSS = 1 and MRS = 1.
Occlusion of a brain vessel leads to a critical reduction in cerebral perfusion and, within minutes, to ischemic infarction with a central infarct core of irreversibly damaged brain tissue and a more or less large area of hypoperfused but still vital brain tissue (the ischemic penumbra), which can be salvaged by rapid restoration of blood flow. Therefore, the underlying rationale for the introduction and application of thrombolytic agents is the lysis of an obliterating thrombus and thus reestablishment of cerebral blood flow by cerebrovascular recanalization with subsequent reperfusion.
Available clot bursting agents include –
Pharmacolgical agents like recombinant tissue plasminogen activator (rtPA)ieAlteplase can be used Intravenous or Intra arterial.
Mechanical clot retrieval or suction thrombectomy devices.
Combination of pharmacologic agent and mechanical agent ie bridging.
Thrombolysis with intravenousalteplase is the primary therapy for acute ischemic stroke. Early administration improves functional outcome, though benefit and risk depend on the time elapsed between stroke onset and initiation of treatment. Randomized controlled trials demonstrated benefit from intravenousthrombolysis when initiated up to 4.5 hours after symptom onset, and pooled analysis of all trials indicates that the sooner that alteplase is given, the greater is the benefit. Treatment carries a risk of bleeding, with symptomatic intracranial hemorrhage (SICH) of around 3%. Initiating treatment after 4.5 hours increases mortality and reverses the risk-benefit balance.
But, opening a clot is not considered as goal of or parameter of stroke recovery, ie recanalization is not reperfusion. This can be attributed to various reasons ie the ischemic penumbra may not exist in the patient, or penumbra may be involving the non eloquent cortex and hence there is no measure of functional recovery.
The success of the use of a clot bursting agent is dependent on various factors which include -
CLOT SITE- Recanalization Rates WITH IV ALTEPLASE (ACTILYSE)
Clot length - MCA clot length > 8 mm has low potential for recanalization with I/V thrombolysis and patients have poor outcome.
Collateral flow - With IV thrombolysis outcomes are better when collateral flow is good. Thrombolytic therapy may act from both sides of the clot when collateral flow is good. Good collateral status was associated with larger penumbra and also increased survival of penumbra
Clot donor – Delineating the mechanism of stroke is the fundamental step in stroke treatment and prevention. Mechanism is largely divided according to TOAST criteria or ICD 10 classification. Donor site needs to be taken into consideration after IV thrombolysis to prevent recurrence of stroke.
We present a case where in, we have used intravenous recombinant tissue plasminogen activator (rtPA) twice within a period of 3 monthsin a patient with intracranial large vessel atherosclerotic disease. In the first stroke – Patient presents to us with moderate stroke with NIHSS = 7. CTA Brain demonstrated a clot in the M1 segment of the right MCA with good collateral flow. The patient satisfied all criteria for IV thrombolysis which was administered. The patient demonstrated early neurological improvement ie Lazarus effect. Lazarus effect (early neurological improvement) in the NIHSS score at 2 hours was a good predictor of recanalization after IV thrombolysis and suggested good functional outcome at 3 months.
The repeat CTA Brain at 24 hrs demonstrated partial recanalisation of the right MCA with moderate flow.
According to guidelines, patient was managed with best medical treatment on anti platelets and statin with control of risk factors ( Hypertension in this patient’s case).
In about three months of original cerebro vascular event, patient represented with a new episode of left hemiparesis. Again the right MCA was found to be occluded at the M1 segment. Guidelines of IV alteplase limit its use (contra indication) within a period of three months of a cerebro vascular event. The patient satisfied this criterion and hence he was once again treated with IV Alteplase. Once again the patient demonstrated the Lazarus effect with remarkable neurologic recovery within first 2 hrs and subsequent 24 hrs. Post IV tPA MRA Brain suggests partial recanalisation with good collateral flow.
In view of intracranial large vessel disease, patient underwent right MCA stenting. The patient is now being followed up in the outpatient dept where he does not report any recurrence or TIA like symptoms.
We present a unique case where in the patient has been treated with IV alteplase twice in a period of three months and has shown remarkable neurologic recovery. No particular guidelines are currently available on the use of IV alteplase for a second time. Is a second treatment with rtPA within three months hazardous? rtPA is cleared rapidly from blood and metabolized mainly by liver. The plasma half life alpha is 4 to 5 minutes and beta half life is about 40 minutes. A marked and prolonged decrease of the circulating fibrinogen level is unusual. Though repeat IV thrombolysis within a short interval may involve a considerable risk of serious hemorrhage, especially in the infracted area, three months is considered to be a safe period for the use of repeat IV thrombolysis according to prescription guidelines.
We will like to stress on delineating the mechanism of stroke and to think beyond the guidelines in particular situations while adhering to them to help patients appropriately.
Keyser JD, Gdovinova Z et al. Intravenous Alteplase for StrokeBeyond the Guidelines and in Particular Clinical Situations. Stroke. 2007; 38: 2612-2618
Alexandrov AV, Grotta JC.Arterial reocclusion in stroke patients treated with intravenous tissue plasminogen activator. Neurology. 2002 Sep 24;59(6):862-7
Topakian R, Gruber F, Fellner FA, Haring HP, Aichner FT. Thrombolysis beyond the guidelines: two treatments in one subject within 90 hours based on a modified magnetic resonance imaging brain clock concept. Stroke 2005 Nov;36(11):e162-4. Epub 2005 Oct 6.
Authors:- Dr.Shirish HastakMD, DM
Consultant Neurologist, Director of Stroke Services, KDAH
Past President of Indian Stroke Association
Dr. Manish Shrivastav, DNB
Head, Interventional Neuroradiology, KDAH
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