Nearly 80% of strokes are due to ischemic cerebral infarction and 20% are caused by hemorrhagic stroke. Over the last 10 years, there were 16.9 million stroke cases, 33.0 million prevalent stroke cases, and 5.9 million deaths attributed to stroke per year, worldwide. The lifetime incidence of stroke for adults is about 25%. In the United States, the annual incidence of stroke is 795.000 patients, of which about 610.000 (77%) are new strokes, and 185.000 (23%) are recurrent cases. (1, 2)

What are the odds of dying from Stroke?

Stroke is the second main disease leading to death and the third leading reason for disability. Stroke leads to 9% of deaths. Stroke leads to 50-100 deaths per 100,000 people, yearly. (3, 4)

In the USA, the annual % change (APC) in stroke deaths changed from a 3.4% decrease yearly from 2000 to 2003, to a 6.6% decrease during the period of 2003-2006, to a 3.1% decrease between 2006 and 2013, to a 2.5% increase per year during the period of 2013-2015. About 25% of ischemic strokes are fatal in the first month, almost one third by 6 months, and a half in the first year. Stroke mortality is higher for those with hemorrhagic stroke, which leads to a 50% mortality in the first month. A serious subtype of hemorrhagic stroke is subarachnoid hemorrhage which causes death in over a third of cases in the first days. (5, 6)

Also, stroke leads to high morbidity in up to 50% of survivors being chronically disabled and have an early retirement. Additionally, vascular dementia is another problem that could occur in nearly 19.6%- 43% of stroke patients. Recurrent stroke is a serious risk and it ranges from 8.3% to 27.9%. (3) 

Stroke can also kill off your finances!

Cost of stroke includes the hospital stay (in stroke unit/ward), drugs, diagnostic radiology, blood tests, physiotherapy, and rehabilitation. The cost was influenced by patient characteristics, treatment given, and care plan that should be considered. Acute-care in the 2 years following a first stroke accounts for 45.0% of the total cost, long-term ambulatory care accounted for 35.0%, and nursing home costs accounted for about 20.0% of the total cost of stroke. (6, 7)

The study of Wang et al., 2014, aimed to determine the cost of hospitalization, between 2006 and 2008. They identified 97,374 hospitalizations with stroke in USA. The average cost per person was $20,396 for ischemic stroke, and hemorrhagic stroke cost $14,499 more than ischemic stroke (P <.001). The cost was higher for younger patients (18-44 years) than for older (45-64).Also, for ischemic stroke, men had a higher cost than women, but the reverse was true for hemorrhagic stroke. Having hypertension, ischemic heart disease, or diabetes as a comorbidity was negatively associated with the costs. (8)

Also, the study of Johnson et al., 2016, was conducted to estimate the costs in the first year following hospitalization for acute ischemic stroke. Average cost per person ranged from $44,929 to $61,354. Approximately 50%–55% of total 12-month costs were incurred between day 31 and day 365 following the event. Nearly a quarter of patients were readmitted within 30 days. The average readmission length of stay was nearly three times that of the initial hospitalization (3.8 vs 10.8 days). (9)

Overall stroke care costs nearly $50 billion yearly; ($31 billion direct costs and $20 billion indirect costs). Also, unemployment, missed work days, and premature mortality extend this figure to a further $ 68.5 billion dollars. This is a large economic burden on the government! (10)

Stroke Prevention works, if you can afford it

For stroke prevention, patients should modify their risk factors. These include hypertension, diabetes, hyperlipidemia, smoking, underlying cardiac, such as atrial fibrillation, and carotid stenosis. Stroke prevention is very essential to decrease the prevelance of stroke. It was observed that uninsured patients have poorer control of stroke risk factors. Also, the number of patients who go to their doctors for stroke prevention is very low, especially among uninsured people. (3, 10, 11)

What is the current health insurance situation in America?

Although the Affordable Care Act has reduced the number of uninsured people in the USA, over 30 million Americans remain uninsured. Also, Medicaid in its current shape is not enough to help stroke patients. Additionally, racial and ethnic minorities are disproportionally impacted by state decisions on Medicaid expansion. Subsequently, the government is required to expand the coverage of people towards stroke national insurance policy. The results of the Oregon Health Study provide evidence on the effect of increasing insurance plans to the public. In 2008, Oregon conducted a lottery to expand their insurance to a small proportion of uninsured, non-disabled adults and their families. If selected, the person and their family had the opportunity to enroll in the insurance program. Results after 2 years, revealed that coverage expansion increased access to and utilization of medical care, also, it helped to decrease some risk factors of stroke. (12)

What is happening Overseas?

The Taiwan government; with a population of twenty-three million people implemented national health insurance (NHI) which offers their citizens almost equal financial access to comprehensive health services and provides all people with financial risk protection. At the same time, it gives patients the right to freely choose their health care provider and for hospitals and physicians to freely choose their practice mode and be paid on a fee-for-service basis. The NHI policy covers a wide range of services, including medical services, laboratory tests, dental care, drugs, and home nurse visits. The health spending increased by 6% on the year of implementing the NHI, then, it dropped sharply after that to become a quarter of the pre-NHI level, after 4 years of the project. (13)

A Country has an obligation to take care of its own people

Stroke is different from every other illness in that it can potentially affect your thinking and your speech and your mental abilities and thereby severely limit what you can do to help yourself. If the breadwinner in a family is affected by stroke, the sheer cost of emergency health care, along with the burden of post stroke care, and the loss of income that is always a danger in a post stroke situation, all combine to make stroke dangerous not just to the individual’s health, but to every dream and hope for that family, with no way out of a crash and burn catastrophic disaster.

Often we see patients who have severe cognitive deficits from stroke, and they cannot even get on disability, because the evaluator looks at them and say “You look fine to me” , not realizing that the brain scan looks like Hiroshima, and not factoring in the truth that if your cognition is upside down and you can’t manage a coherent stream of thought and action, no matter how ‘fine’ you look you simply are not employable.

The government cannot solve everything, but if emergency stroke care were to be backed by an universal government backed insurance, it would

change the already frightening stroke scenario from an all-ending catastrophe to one that can have a positive outcome. It would make patients more likely to seek prompt care, as opposed to trying to walk it off or sleep it off to try and avoid the financial danger that looms overhead the moment a patient cross the doorway of the Emergency Room.

If you agree with these views please share this article.

References:

1- Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, et al, Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association. Circulation. 2020;141(9):e139. Epub 2020 Jan 29. 

2- Feigin VL, Nguyen G, Cercy K, Johnson CO, GBD 2016 Lifetime Risk of Stroke Collaborators, et al, Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016. N Engl J Med. 2018;379(25):2429. 

3-Piliszek A, Witkowski G, Sklinda K, Szary C, Ryglewicz D, Dorobek M, et al. Comprehensive imaging of stroke – Looking for the gold standard. Neurol Neurochir Pol. 2016 Jul-Aug. 50 (4):241-50. 

4-Yang Q; Tong X; Schieb L; Vaughan A; Gillespie C; Wiltz JL; King SC; Odom E; Merritt R; Hong Y; George MG, Vital Signs: Recent Trends in Stroke Death Rates – United States, 2000-2015. MMWR Morb Mortal Wkly Rep.  2017; 66(35):933-939.

5-Mullins ME, Lev MH, Schellingerhout D, Gonzalez RG, Schaefer PW. Intracranial hemorrhage complicating acute stroke: how common is hemorrhagic stroke on initial head CT scan and how often is initial clinical diagnosis of acute stroke eventually confirmed?. AJNR Am J Neuroradiol. 2005 Oct. 26(9):2207-12.

6- Yukihiro Y, Uehara T,  Yamasaki H, et al, Hospital-Based Study of the Care and Cost of Acute Ischemic Stroke in Japan. Stroke 2003; Volume 34, Issue 3, 1 March, Pages 718-724

7- Ingall T; Stroke—Incidence, Mortality, Morbidity and Risk . J Insur Med 2004;36:143–152

8-Wang G,  Zhang Z,  Ayala C, Dunet DO, et al, Costs of Hospitalization for Stroke Patients Aged 18-64 Years in the United States. J Stroke Cerebrovasc Dis. 2014 May-Jun; 23(5): 861–868.

9-Johnson B, Bonafede M, Watson C; Short- and longer-term health-care resource utilization and costs associated with acute ischemic stroke.  ClinicoEconomics and Outcomes Research. 2016; Volume 2016:8 Pages 53—61. DOIhttps://doi.org/10.2147/CEOR.S95662

10- Ayanian JZ, Zaslavsky AM, Weissman JS, Schneider EC, Ginsburg JA. Undiagnosed hypertension and hypercholesterolemia among uninsured and insured adults in the Third National Health and Nutrition Examination Survey. Am J Public Health. 2003;93:2051–2054. 

11- Epestein D, Mason A, Manca A; The hospital costs of care for stroke. Health Econ. 2008; 17: S21–S31. DOI: 10.1002/hec.1329

12- Finkelstein A, Taubman S, Wright B, Bernstein M, Gruber J, Newhouse JP, et al. The oregon health insurance experiment: Evidence from the first year. The Quarterly Journal of Economics. 2012;127:1057–1106.

13-J.R. Lu, JR, Hsiao WC, “Development of Taiwan’s National Health Accounts,” , 2001, no. 4: 547 –576.

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The majority of trials did not show major bleeding or rupture of aneurysms following TPA infusion. Only 3-5% of cases had a subarachnoid hemorrhage. (3, 4, 5)

Also, limited data suggest that intravenous thrombolysis with recombinant TPA appears safe in patients with unruptured intracranial aneurysms who have an acute ischemic stroke. (5)

The risk of bleeding is minimal for patients with small aneurysms <5 mm in diameter.

Also, to minimize the risk of bleeding, some trials used TPA intra-arterially rather than intravenous, other trials used the dose of TPA for myocardial infarction; 0.6 mg/kg. (6, 7, 8)

The currently available guideline from American Heart Association/American Stroke Association suggests that patients who are known to harbor a small or moderate-sized (<10 mm), unruptured and unsecured intracranial aneurysm, could be considered for TPA, and the use of IV alteplase in such patients is reasonable and probably recommended. (9)

References :

1-The National Institute of Neurological Disorders and Stroke rtPA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995; 333:1581–1587.

2- Adeoye O, Hornung R, Khatri Pooja, Kleindorfer D. Recombinant tissue-type plasminogen activator use for ischemic stroke in the United States: a doubling of treatment rates over the course of 5 years. Stroke. 2011; 42:1952–1955.

3-Fang MC, Cutler DM, Rosen AB. Trends in thrombolytic use for ischemic stroke in the United States. J Hosp Med. 2010; 5:406–409.

4-Aleu A, Mellado P, Lichy C, Kohrmann M, Schellinger P. Hemorrhagic complications after off-label thrombolysis for ischemic stroke. Stroke. 2007; 38:417–422.

5-De Silva DA, Manzano J, Chang HM, Wong MC. Reconsidering recent myocardial infarction as a contraindication for IV stroke thrombolysis. Neurology. 2011; 76:1838–1840.

6-Lagares A, Gomez PA, Lobato RD, Alen JF, Campollo J, Benito-Leon J. Cerebral aneurysm rupture after rtPA thrombolysis for acute myocardial infarction. Surg Neurol. 1999; 52:623–626.

7-De Keyser J, Gdovinova Z, Uyttenboogaart M, Vroomen PC, Luijckx GJ. Intravenous alteplase for stroke: beyond the guidelines and in particular clinical situations. Stroke. 2007; 38:2612–2618.

8-Kim J, Park M, Yoon W, Cho K. Detection and significance of incidental unruptured cerebral aneurysms in patients undergoing intravenous thrombolysis for acute ischemic stroke. J Neuroimaging. Epub ahead of print December 9, 2010.

9-Powers WJ, Rabinstein AA, Ackerson T, et al, on behalf of the American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association Reviewed for evidence-based integrity and endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons Endorsed by the Society for Academic Emergency Medicine and Neurocritical Care Society The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke is available at http://stroke.ahajournals.org. Downloaded from http://ahajournals.org by on December 19, 2020. DOI: 10.1161/STR.0000000000000158

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History of previous intracranial hemorrhage is a contraindication for the application of tPA, as per currently available guidelines. (1, 2)

However, recent studies showed that this contraindication is very strict and that some patients did not receive effective treatment because of that. The use of intravenous thrombolysis is supported by an increasing number of studies. However, the ability of stroke patients with a history of cerebral hemorrhage to accept tPA thrombolytic therapy remains in question, and the safety of this treatment requires further evaluation taking into consideration that there is a potential risk of subarachnoid hemorrhage after thrombolysis therapy. (1, 2)

Additionally, for safety, patients with a history of intracranial bleeding could be treated with a low dose of tPA (0.6 mg/kg), as per Japanese evidence. Japan Alteplase Clinical Trial (J-ACT) suggested that a low dose of tPA (0.6 mg/kg) intravenous thrombolytic therapy could obtain similar clinical efficacy, reduce the risk of bleeding including subarachnoid hemorrhage, and could reduce mortality post tPA, compared to the standard dose (0.9 mg/kg). (3, 4, 5, 6)

Also, the currently available guideline from American Heart Association/American Stroke Association suggests that TPA is contraindicated in patients with a history of intracranial bleeding. (7)

References:

1- van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol. 2010;9:167–176.

2- Romano JG, Smith EE, Liang L, Gardener H, Camp S, Shuey L, et al. Outcomes in mild acute ischemic stroke treated with intravenous thrombolysis: a retrospective analysis of the get with he guidelines-stroke registry. JAMA Neurol. 2015;72:423–431. doi: 10.1001/jamaneurol.2014.4354.

3- Cronin CA, Shah N, Morovati T, Hermann LD, Sheth KN. No increased risk of symptomatic intracerebral hemorrhage after thrombolysis in patients with European Cooperative Acute Stroke Study (ECASS) exclusion criteria. Stroke. 2012;43:1684–1686. doi: 10.1161/STROKEAHA.112.656587. 

4-Steiner T, Al-Shahi Salman R, Beer R, Christensen H, Cordonnier C, Csiba L, et al. European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage. Int J Stroke. 2014;9:840–855.

5- De Keyser J, Gdovinova Z, Uyttenboogaart M, Vroomen PC, Luijckx GJ. Intravenous alteplase for stroke: beyond the guidelines and in particular clinical situations. Stroke. 2007;38:2612–2618.

6-Tsivgoulis G, Safouris A, Alexandrov AV. Safety of intravenous thrombolysis for acute ischemic stroke in specific conditions. Expert Opin Drug Saf. 2015;14:845–864. 

7-Powers WJ, Rabinstein AA, Ackerson T, et al, on behalf of the American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association Reviewed for evidence-based integrity and endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons Endorsed by the Society for Academic Emergency Medicine and Neurocritical Care Society The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke is available at http://stroke.ahajournals.org. Downloaded from http://ahajournals.org by on December 19, 2020. DOI: 10.1161/STR.0000000000000158

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Patients should have an acute ischemic stroke caused by a large artery occlusion in the proximal anterior circulation and are evaluated at the stroke center with available expertise, or who can be transferred to such centers. (1, 2, 3)

Eligibility criteria based upon the DAWN trial for those who present within 6 – 24 hours last known to be at neurological baseline are as follows:

-Failed or contraindicated for intravenous TPA, 

-A deficit on the NIHSS of ≥10 points,  

-No significant pre-stroke disability: baseline modified Rankin scale (mRS) score ≤1,

-Baseline infarct involving less than one-third of the territory of the MCA on CT or MRI, 

-Intracranial arterial occlusion of the ICA or the M1 segment of the MCA, 

-A clinical-core mismatch according to age; If age ≥80 years: NIHSS ≥10 and an infarct volume <21 mL, and for age <80 years: NIHSS 10- 19 and an infarct volume <31 mL, or for age <80 years: NIHSS ≥20 and an infarct volume <51 mL. (4, 5, 6, 7)

The currently available guideline from American Heart Association/American Stroke Association suggests that DAWN criteria for mechanical thrombectomy are applied for those present between 16- 24 hours from last known to be at neurological baseline. (7)

References:

1-Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015;372:2285-2295.

2-Bracard S, Ducrocq X, Mas JL, et al. Mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke (THRACE): a randomised controlled trial. Lancet Neurol 2016;15:1138-1147.

3-Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016;387:1723-1731.

4-Saver JL, Goyal M, van der Lugt A, et al. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA 2016;316:1279-1288.

5-Dávalos A, Blanco M, Pedraza S, et al. The clinical-DWI mismatch: a new diagnostic approach to the brain tissue at risk of infarction. Neurology 2004;62:2187-2192.

6-Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, Yavagal DR, Ribo M, Cognard C, Hanel RA, Sila CA, Hassan AE, Millan M, Levy EI, Mitchell P, Chen M, English JD, Shah QA, Silver FL, Pereira VM, Mehta BP, Baxter BW, Abraham MG, Cardona P, Veznedaroglu E, Hellinger FR, Feng L, Kirmani JF, Lopes DK, Jankowitz BT, Frankel MR, Costalat V, Vora NA, Yoo AJ, Malik AM, Furlan AJ, Rubiera M, Aghaebrahim A, Olivot JM, Tekle WG, Shields R, Graves T, Lewis RJ, Smith WS, Liebeskind DS, Saver JL, Jovin TG, DAWN Trial Investigators. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018;378(1):11. Epub 2017 Nov 11.

7-Powers WJ, Rabinstein AA, Ackerson T, et al, on behalf of the American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association Reviewed for evidence-based integrity and endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons Endorsed by the Society for Academic Emergency Medicine and Neurocritical Care Society The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke is available at http://stroke.ahajournals.org. Downloaded from http://ahajournals.org by on December 19, 2020. DOI: 10.1161/STR.0000000000000158

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To qualify for mechanical thrombectomy; patients should have an ischemic stroke caused by a large artery occlusion in the proximal anterior circulation and are evaluated at a stroke center, or who can be transferred to such centers. Such patients should be considered for mechanical thrombectomy when DEFUSE3 criteria are fulfilled. (1, 2)

The DEFUSE 3 trial selects patients for treatment if they present between 6- 16 hours. 

DIFFUSE3 eligibility criteria are as follows:

A deficit on the NIHSS of ≥6 points, 

-Only slight or no pre stroke disability: baseline Modified Rankin Scale (mRS) score ≤2,

-Arterial occlusion of the cervical or intracranial ICA (with or without tandem MCA lesions) or the M1 segment of the MCA demonstrated on MR angiography or CT angiography,

A target mismatch profile on CT perfusion or MRI defined as an ischemic core volume <70 ml, a mismatch ratio (the volume of the perfusion lesion divided by the volume of the ischemic core) >1.8, and a mismatch volume (volume of perfusion lesion minus the volume of the ischemic core) >15 mL, and

Age 18 to 90 years. (3, 4)

For patients who fulfill the above criteria, mechanical thrombectomy is recommended. (5, 6, 7)

The currently available guideline from American Heart Association/American Stroke Association suggests that DIFFUSE3 criteria for mechanical thrombectomy are applied for those present between 6- 16 hours. (7)

References:

1- Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016;387:1723-1731.

2-Powers WJ, Derdeyn CP, Biller J, et al. 2015 American Heart Association/American Stroke Association focused update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2015;46:3020-3035.

3-Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med 2018;378:11-21.

4-Wheeler HM, Mlynash M, Inoue M, et al. Early diffusion-weighted imaging and perfusion-weighted imaging lesion volumes forecast final infarct size in DEFUSE 2. Stroke 2013;44:681-685.

5- Albers GW: Use of Imaging to Select Patients for Late Window Endovascular Therapy. Stroke. 2018;49(9):2256. 

6- Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, McTaggart RA, Torbey MT, Kim-Tenser M, Leslie-Mazwi T, Sarraj A, Kasner SE, Ansari SA, Yeatts SD, Hamilton S, Mlynash M, Heit JJ, Zaharchuk G, Kim S, Carrozzella J, Palesch YY, Demchuk AM, Bammer R, Lavori PW, Broderick JP, Lansberg MG, DEFUSE 3 Investigators. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med. 2018;378(8):708. Epub 2018 Jan 24.

7-Powers WJ, Rabinstein AA, Ackerson T, et al, on behalf of the American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association Reviewed for evidence-based integrity and endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons Endorsed by the Society for Academic Emergency Medicine and Neurocritical Care Society The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke is available at http://stroke.ahajournals.org. Downloaded from http://ahajournals.org by on December 19, 2020. DOI: 10.1161/STR.0000000000000158

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Because the benefit of alteplase is time-dependent, it is essential to treat patients as quickly as possible. Eligible patients should receive intravenous alteplase without delay even if mechanical thrombectomy is being considered. (1)

Mechanical thrombectomy is indicated for patients with acute ischemic stroke due to a large artery occlusion in the anterior circulation who can be treated within 24 hours of the time last known to be well, regardless of whether they receive intravenous TPA.

Two issues may limit the widespread application of mechanical thrombectomy. 

Firstly, only 10% of patients with acute ischemic stroke have a proximal large artery occlusion in the anterior circulation and present early enough to qualify for mechanical thrombectomy. 

Secondly, only a few stroke centers have sufficient resources and expertise to deliver this therapy. (2, 3)

Patient inclusion criteria:

Patients should fulfill all the following eligibility criteria; 

– Patients with proximal large artery occlusion in the anterior circulation, 

-Patients present within 6 hours of the time they were last known to be at their neurological baseline,  

-Neuroimaging with CT head without contrast or diffusion-weighted MRI is consistent with a small infarct area and rules out intracranial bleeding

– CT Angiography/ MR angiography shows a proximal large artery occlusion in the anterior circulation

Thrombectomy should be performed at a stroke center with appropriate expertise in the use of stent retrievers

-The patient has a persistent, potentially disabling neurologic deficit. (4)

For patients who can start treatment through a femoral puncture within 6 hours of symptom onset, the following additional eligibility criteria can be uses, which is modified from the MR CLEAN trial:

1- Patients should have a clinical diagnosis of acute stroke

2- A deficit on the National Institutes of Health Stroke Scale (NIHSS) of ≥6 points or any persistent neurologic deficit that is potentially disabling 

3- An Alberta Stroke Program Early CT Score (ASPECTS) score ≥6 on non-contrast CT brain or diffusion-weighted MRI. The ASPECTS method divides the middle cerebral artery (MCA) territory into 10 regions of interest;

Subcortical structures are allotted three points: one each for the caudate, lentiform nucleus, and internal capsule.

MCA cortex is allotted seven points:

-Four of these points come from the axial CT cut at the level of the basal ganglia, with one point for the insular cortex and one point each for M1, M2, and M3 regions (anterior, lateral, and posterior MCA cortex).

-Three points come from the CT cut just rostral to the basal ganglia, with one point each for M4, M5, and M6 regions (anterior, lateral, and posterior MCA cortex).

-One point is subtracted for an area of early ischemic change, such as focal swelling or parenchymal hypoattenuation, for each of the defined regions.

Thus, a normal CT scan has an ASPECTS value of 10 points, while diffuse ischemic change throughout the MCA territory gives a value of 0.

4- CT angiography or MR Angiography shows intracranial arterial occlusion of the distal intracranial internal carotid artery (ICA), or the M1 or M2 segments of the middle cerebral artery (MCA), or the A1 or A2 segments of the anterior cerebral artery (ACA).

6-Age ≥18 years, 

7-Patients should be functioning independently before stroke onset, and 

8- Evidence of moderate-to-good collateral circulation, defined as the filling of ≥50 percent of the MCA territory pial circulation on CT angiography. (5, 6, 7)

To note, the currently available guideline from American Heart Association/American Stroke Association suggests more selective criteria for mechanical thrombectomy to adults with no significant pre-stroke disability (a modified Rankin Scale [mRS] score of ≤1), a causative occlusion of the ICA or the M1 segment of the MCA, NIHSS score of ≥6, ASPECT score ≥6, and treatment starts within 6 hours of symptom onset. The guideline states that benefits are uncertain for patients who have an NIHSS score <6, a pre-stroke mRS score >1, or a larger infarct core (ASPECTS score <6). (8, 9)

Exclusion criteria include all other scenarios. 

References:

1-Saver JL, Goyal M, van der Lugt A, Menon BK, Majoie CB, Dippel DW, et al. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA 2016;316: 1279-1288.

2- Bang OY, Goyal M, Liebeskind DS. Collateral circulation in ischemic stroke: assessment tools and therapeutic strategies. Stroke 2015;46: 3302-3309.

3- Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, et al. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet 1998;352:1245-1251.

4- Smith EE, Saver JL, Cox M, Liang L, Matsouaka R, Xian Y, et al. Increase in endovascular therapy in Get With The Guidelines-Stroke after the publication of the pivotal trials. Circulation 2017;136:2303- 2310.

5- Evans JW, Graham BR, Pordeli P, Al-Ajlan FS, Willinsky R, Montanera WJ, et al. Time for a time window extension: insights from late presenters in the ESCAPE trial. AJNR Am J Neuroradiol 2018;39:102-106.

6- Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015;372:2296-2306.

7- Telischak NA, Wintermark M. Imaging predictors of procedural and clinical outcome in endovascular acute stroke therapy. Neurovasc Imaging 2015;1:4. 14. Albers GW. Late window paradox. Stroke 2018;49:768-771.

8- Badhiwala JH, Nassiri F, Alhazzani W, Selim MH, Farrokhyar F, Spears J, et al. Endovascular thrombectomy for acute ischemic stroke: a meta-analysis. JAMA 2015;314:1832-1843. 17. Vidale S, Agostoni E. Endovascular treatment of ischemic stroke: an updated meta-analysis of efficacy and safety. Vasc Endovascular Surg 2017;51:215-219.

9-Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2018;49:e46-e110

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-In patients who have not recently used oral anticoagulants or heparin, TPA can be started before the availability of coagulation test results. And TPA to be discontinued if the pre-treatment INR is greater than 1.7, the aPTT is elevated above 1.5 of upper normal limit (>40) or platelet count <100.000. (1, 2)

-For patients with inadequate historical information, alteplase therapy should not be started until the INR, aPTT results are available.

Premature data suggest that a normal coagulation profile can be expected upon arrival to the emergency department by assessing three questions:

Is the patient not taking an oral anticoagulant?

Is the patient not taking heparin or low molecular weight heparin?

Is the patient not on hemodialysis? (3, 4)

-For patients on oral anticoagulant/heparin, please refer to TPA on patients on anticoagulation therapy.

The currently available guideline from American Heart Association/American Stroke Association suggests that platelet count, INR, and aPTT, results may be necessary for some circumstances if there is suspicion of coagulopathy. While delaying TPA waiting for hematological or coagulation test results if there is no reason to suspect an abnormal test, is not recommended. (5)

References:

1-Kulairi Z, Deol N, Tolly R, Manocha R, Naseer M. Is Intravenous Heparin a Contraindication for TPA in Ischemic Stroke? Case Rep Neurol Med. 2017;2017:9280961. 

2-Salazar AJ, Useche N, Granja M, Morillo AJ, Bermúdez S. Ruling Out Brain CT Contraindications prior to Intravenous Thrombolysis: Diagnostic Equivalence between a Primary Interpretation Workstation and a Mobile Tablet Computer. Int J Telemed Appl. 2017;2017:6869145.

3-Gottesman RF, Alt J, Wityk RJ, Llinas RH: Predicting abnormal coagulation in ischemic stroke: reducing delay in rt-PA use. Neurology. 2006;67(9):1665.

4- Rost NS, Masrur S, Pervez MA, Viswanathan A, Schwamm LH: 

Unsuspected coagulopathy rarely prevents IV thrombolysis in acute ischemic stroke. Neurology. 2009;73(23):1957. Epub 2009 Nov 25. 

5-Powers WJ, Rabinstein AA, Ackerson T, et al, on behalf of the American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association Reviewed for evidence-based integrity and endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons Endorsed by the Society for Academic Emergency Medicine and Neurocritical Care Society The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke is available at http://stroke.ahajournals.org. Downloaded from http://ahajournals.org by on December 19, 2020. DOI: 10.1161/STR.0000000000000158

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-Oral anticoagulants, other than DOAC and Heparin:

Current anticoagulant use with evidence of anticoagulant effect by laboratory tests is a contraindication to TPA. 

For patients without recent use of oral anticoagulants or heparin, treatment with TPA could be considered before the availability of coagulation test results. In such scenario, TPA treatment should be discontinued if [international normalized ratio (INR) >1.7, activated partial thromboplastin time (aPTT) >1.5 above normal limit (>40), or platelet count <100.000]. (1, 2)

-Patients on DOAC agents:

DOAC use is a contraindication to TPA unless laboratory tests such as PT, INR, aPTT, platelet count are normal or the patient did not receive a DOAC dose for more than 48 hours, assuming normal renal function. However, recent evidence shows that recent use of DOAC is not associated with an increased risk of symptomatic intracerebral hemorrhage following TPA infusion. 

DOAC reversal might be an option to safely treat the patient with TPA, although this approach is not yet considered as safe. Dabigatran reversal is with idarucizumab. (3, 4)

Alternative options:

For patients whose the last dose of DOAC is earlier than 48 hours, guidelines encourage considering mechanical thrombectomy instead of TPA. Also, recently, a Japanese guideline-recommended TPA and minimized the interval from the last dose of DOAC intake to 4 hours and recommended 0.6 mg/kg alteplase instead of the standard 0.9 mg/kg. 

(5, 6, 7)

The currently available guideline from American Heart Association/American Stroke Association suggests that patients on therapeutic (not prophylactic) LMWH within the previous 24 hours are a contraindication to TAP. Those on DOAC should not receive TPA unless they have not received a dose of these agents for >48 hours if they have a normal renal function, or aPTT, INR, platelet count, clotting time, thrombin time, and appropriate direct factor Xa activity assays are normal. (7)

References:

1- Shahjouei S, Tsivgoulis G, Bavarsad Shahripour R, Jones GM, Alexandrov AV, Zand R. Safety of intravenous thrombolysis among stroke patients taking new oral anticoagulants– case series and systematic review of reported cases.J Stroke Cerebrovasc Dis. 2015; 24:2685–2693.

2- Xian Y, Federspiel JJ, Hernandez AF, Laskowitz DT, Schwamm LH, Bhatt DL, et al.. Use of intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke who take non-vitamin K antagonist oral anticoagulants before stroke.Circulation. 2017; 135:1024–1035.

3-Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al.; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.N Engl J Med. 2011; 365:883–891. doi: 10.1056/NEJMoa1009638.

4- Seiffge DJ, Traenka C, Polymeris AA, Thilemann S, Wagner B, Hert L, et al.. Intravenous thrombolysis in patients with stroke taking rivaroxaban using drug specific plasma levels: experience with a standard operation procedure in clinical practice.J Stroke. 2017; 19:347–355.

5- Seiffge DJ, Hooff RJ, Nolte CH, Béjot Y, Turc G, Ikenberg B, et al.; NOACISP Study Group. Recanalization therapies in acute ischemic stroke patients: impact of prior treatment with novel oral anticoagulants on bleeding complications and outcome.Circulation. 2015; 132:1261–1269.

6- Toyoda K, Yamagami H, Koga M. Consensus guides on stroke thrombolysis for anticoagulated patients from Japan: application to other populations.J Stroke. 2018; 20:321–331. doi: 10.5853/jos.2018.01788.

7- Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al.; American Heart Association Stroke Council. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.Stroke. 2018; 49:e46–e110

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Few points that help to distinguish Todd’s paralysis include;

-Todd’s paralysis is observed after partial seizures or generalized tonic-clonic seizures.

-The probability of Todd’s paralysis is higher if epilepsy is associated with old age or a history of stroke.

-The etiology of Todd’s paralysis is associated with cerebral perfusion abnormality after seizures.

-The duration of Todd’s paralysis range from minutes to days, based on the type of seizure or if the patient experienced cortical structural damage. (3, 4)

The misdiagnosis of TPA as a limb weakness after acute ischemic stroke may result in unnecessary use of TPA, which is contraindicated for patients with neurological deficits. However, the administration of TPA in patients with a seizure at onset is reasonable if the deficits are thought to be related to stroke and not postictal episodes. (5, 6)

Also, the currently available guideline from American Heart Association/American Stroke Association suggests that the use of IV alteplase is reasonable in patients with a seizure at the onset of acute stroke if evidence suggests that residual impairments are secondary to stroke and not a postictal phenomenon. (7)

References:

1-Binder DK. A history of Todd and his paralysis. Neurosurgery. 2004;54(2):480–86. discussion 486–87.

2- Mastriana J, Pay JL, Taylor RS. Todd paresis. StatPearls; Treasure Island (FL): 2019. 

3- Meyer JS, Portnoy HD. Post-epileptic paralysis a clinical and experimental study. Brain. 1959;82(2):162–85. 

4- Werhahn KJ. Weakness and focal sensory deficits in the postictal state. Epilepsy Behav. 2010;19(2):138–39. 

5- Powers WJ, Rabinstein AA, Ackerson T et al: Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke, 2019; 50(12): e344–418

6- Gallmetzer P, Leutmezer F, Serles W, et al. Postictal paresis in focal epilepsies – incidence, duration, and causes: A video-EEG monitoring study. Neurology. 2004; 62(12):2160–64. 

7-Powers WJ, Rabinstein AA, Ackerson T, et al, on behalf of the American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association Reviewed for evidence-based integrity and endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons Endorsed by the Society for Academic Emergency Medicine and Neurocritical Care Society The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke is available at http://stroke.ahajournals.org. Downloaded from http://ahajournals.org by on December 19, 2020. DOI: 10.1161/STR.0000000000000158

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The overall safety of TPA in infective endocarditis is unknown, unproven and the guidelines are silent as to whether or not infective endocarditis is a contraindication to TPA therapy. (1, 2)

Available literature reflects variable outcomes tom TPA therapy. Some case reports showed that infective endocarditis patients treated with TPA had positive outcomes, while other case series revealed that patients had intracranial hemorrhage and death. (3, 4)

Other points to be considered; 

-Early recognition:

To distinguish infective endocarditis-related stroke from other embolic strokes in the acute setting, an ECHO cardiogram and blood culture are essential. The obvious difficulty of basing the diagnosis of infective endocarditis on the modified Duke criteria is that it relies on test results not obtainable within hours of presentation, so patients could be out of the TPA window. Physicians must therefore rely primarily on other factors to determine the likelihood of infective endocarditis. (5)

When to suspect:

Fever on presentation in the setting of valve replacement increases the suspicion of infective endocarditis. 

A new heart murmur is also concerning for infective endocarditis. 

Leukocytosis and anemia, the most common laboratory abnormalities, are not specific to infective endocarditis and must be considered in the clinical context. (6, 7)

-Other points to be considered; 

-A history of valve replacement in the absence of other clinical signs of infective endocarditis should not preclude TPA therapy.

-Antibiotic therapy for endocarditis is critical to reducing the risk of first and recurrent ischemic strokes. Early initiation of antibiotic therapy reduces the risk of embolization significantly. This antibiotic treatment is likely to be empirical at first, then modified according to the culture result. (7, 8)

The currently available guideline from American Heart Association/American Stroke Association suggests that for patients with stroke and infective endocarditis, treatment with TPA should not be administered because of the increased risk of intracranial bleeding. (9)

References:

1- Hart RG, Foster JW, Luther MF, Kantar MC. Stroke in infective endocarditis. Stroke. 1990;21(5):695–700 

2- Ruttmann E, Willeit J, Ulmer H, et al. Neurological outcome of septic cardioembolic stroke after infective endocarditis. Stroke. 2006;37(8):2094–2099.

3- Sontineni SP, Mooss AN, Andukuri VG, Schima SM, Esterbrooks D. Effectiveness of thrombolytic therapy in acute embolic stroke due to infective endocarditis. Stroke Res Treat. Epub ahead of print, Nov 9, 2009 

4-Bhuva P, Kuo SH, Claude Hemphill J, Lopez GA. Intracranial hemorrhage following thrombolytic use for stroke caused by infective endocarditis. Neurocrit Care. 2010;12(1):79–82 

5- Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000;30(2 pt 1):633–638

6- Junna M, Lin CC, Espinosa RE, Rabinstein AA. Successful intravenous thrombolysis in ischemic stroke caused by infective endocarditis. Neurocrit Care. 2007;6(2):117–120

7- Siccoli M, Benninger D, Schuknecht B, Jenni R, Valavanis A, Bassetti C. Successful intra-arterial thrombolysis in basilar thrombosis secondary to infectious endocarditis. Cerebrovasc Dis. 2003;16(3):295–297

8- Jauch EC, Cucchiara B, Adeoye O, et al. Part 11: adult stroke: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2010;122(18 suppl 3):S818–S828.

9-Powers WJ, Rabinstein AA, Ackerson T, et al, on behalf of the American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association Reviewed for evidence-based integrity and endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons Endorsed by the Society for Academic Emergency Medicine and Neurocritical Care Society The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke is available at http://stroke.ahajournals.org. Downloaded from http://ahajournals.org by on December 19, 2020. DOI: 10.1161/STR.0000000000000158

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