beautiful stroke Case presentation,approach and treatment from NEJM article has been discussed here

1. Elderly Woman with Sudden Hemiplegia
and Aphasia during a Transatlantic Flight.
New England Journal of Medicine. 374(17):1671-1680,
April 28, 2016
Dr. Dipak S Patade
DMH,Pune
“STROKE OF LUCK”

2. Presentation of Case.
• 49/Female
• sudden onset of hemiplegia and aphasia during a
transatlantic flight
• severe weakness developed on the right side and she
lost the ability to speak.
• well until approximately 2 hours before presentation
• The pilot accelerated the aircraft to arrive in Boston
within 2 hours after symptom onset.

3. Clinical findings on her arrival at the airport
• Conscious
• blood pressure : 146/82 mm Hg,
• pulse 100 beats per minute and regular,
• right facial droop and unable to lift her right arm.
• R BSL: 151 mg/dl
• Shifted to further hospital in view of ?Stroke

4. O/E
• alert ,conscious
• followed simple commands but answered “yup” to all
questions.
• Afebrile
• BP :146/77 mm Hg, P: 121 beats per minute,
• RR: 22 breaths per minute,
• Spo2: 96% through NRB mask 4 lit/min,
• pupils : 3 mm and reactive to light.
• left-gaze preference
• mild right facial droop.
• right arm : flaccid (power 0 /5)
• right leg : mild weakness (power 4-/5).
• The strength on the left side and the remainder of
neurological examination were normal.
• Nil significant systemic signs

5. History.
• Past h/o : migraine headaches, asthma, and recurrent
intermittent swelling of her left thigh every few months since
childhood, when she had undergone the surgical excision of a
birthmark on the left inner thigh that had frequently bled.
• Regular medications:
1.aspirin several days per week (for headaches)
2.Asthma inhalers.
• no known allergies except a severe reaction to contrast
material during childhood.
• Non smoker
• No F/H/O of hematologic disease or coagulation
abnormalities.

6. Lab.
Parameter results
Haemogram Normal except TLC-11,900/cmm (N-
76.3%)
Renal function tests normal
R BSL 151 mg/dl
The troponin T level 0.23 ng/ml
Prothrombin time with INR, fibrinogen,
total homocysteine, thyrotropin,β2-
glycoproteins
normal
Serum electrolytes including calcium,
magnesium
normal
ECG Sinus tachycardia
Lipid profile including Lip(a) normal
Provisional diagnosis:
Acute ischemic stroke due to occlusion of the left middle cerebral artery was
made.

7. Further evluation of stroke
• NIHSS score was 14.
(on a scale of 0 to 42, with higher scores indicating
more severe deficit)
• CT brain - revealed mild loss of gray–white
differentiation in the left insula, hyperdensity of the
proximal left middle cerebral artery and the terminus
of the left internal carotid artery, a small hypodensity
in the left thalamus, and no evidence of intracerebral
hemorrhage or mass lesion.

8. Further management.
• A bolus of 5.4 mg of tissue plasminogen activator (t-PA) was
administered i/v 13 minutes after the patient’s arrival, and
then an infusion of 52.2 mg of t-PA was administered over a 1-
hour period, for a total of 0.9 mg of t-PA per kilogram of body
weight.
• CT angiography of the head and neck performed immediately
after the bolus of t-PA was administered, revealed :
• a diminutive proximal left internal carotid artery and no
enhancement of the left internal carotid artery as it entered
the base of the skull
• thrombus in the left paraclinoid and supraclinoid internal
carotid artery that extended into the left middle cerebral
artery (M1 and proximal M2 segments), with reconstitution of
the sylvian branches and prominent collateral vessels.

9. A CT angiogram of the head shows occlusion of the intracranial internal carotid artery
and the left middle cerebral artery (arrow), with reconstitution of the sylvian branches
and prominent collateral vessels.
A diffusion-weighted MRI image of the head (Panel B) shows a small region of
restricted diffusion involving the left insula (arrow).
An angiogram of the left common carotid artery in the frontal view, obtained after
thrombectomy (Panel C), shows normal opacification of the left internal carotid artery
and middle cerebral artery.

10. Further Imaging
• MRI of the head including (DWI) revealed :
• restricted diffusion involving the left insula ,
posterior limb of the left internal capsule, and left
medial temporal lobe,
• in the left frontal and parietal lobes and the right
frontal lobe near the vertex;
• these findings are consistent with infarction
involving the territory of the left middle cerebral
artery.
• The volume of the diffusion abnormality was less
than 25 ml, and therefore the patient was likely to
benefit from endovascular thrombectomy.

11. Further decisions..
• On fluid-attenuated inversion recovery images
(FLAIR ) similar findings as seen on CT angiography
• The presence of a focal area of susceptibility effect in the
proximal left middle cerebral artery was consistent with the
occlusive thrombus in the middle cerebral artery
• The NIHSS score was unchanged despite the administration of
t-PA hence taken for endovascular thrombectomy. The left
internal carotid artery, anterior cerebral artery, and middle
cerebral artery were successfully recanalized.
• On examination at the end of the procedure, the patient had
mild difficulty with simple arithmetic but no other neurologic
deficits; the NIHSS score was 0.

12. Important aspects of Stroke manegement of
this patient.
• Immediate recognition of stroke s/s by husband
• Quick transportation by pilot within 2 hours
• Recognition of stroke by Boston Logan International
Airport EMS team by Use of Cincinnati Prehospital
Stroke Scale- a stroke screening for three symptoms
(facial droop, arm drift, and speech disturbance)
• Transportation to a state-certified stroke center with
prearrival notification through a radio call.
• received t-PA within 3 hours after symptom onset
including of imaging studies(patient received t-PA
within 13 minutes after arrival)

13. Important aspects of Stroke manegement of
this patient.
• intravenous t-PA is ineffective in most patients with
proximal-artery occlusions.
• In such patients, additional treatment with
mechanical thrombectomy devices has been shown
to be beneficial in several large, randomized trials.
• She achieved successful recanalization within 45
minutes of arival With a remarkable recovery to an
NIHSS score of 0.
• Recanalization was completed well before the
recommended target of 2 hours after arrival at the
emergency department.

14. Evaluation for the Cause of Stroke
• Patient had chest discomfort and severe shortness of
breath just before the onset of weakness, which the crew
believed to be a panic attack.
• Clues:
1.tachypnea at rest before the onset of stroke,
2.the occurrence of the stroke during airplane travel,
3.the unexplained elevated troponin level along with
normal results on echocardiography,
4.the childhood history of a vascular abnormality
in the left thigh.
• ??? venous thromboembolism as a source of
paradoxical embolism.

15. Causes.
• In a young patient (<50 years of age) such as this
one, with no traditional vascular risk factors and a
large clot burden,we must broaden the search:
1.thrombophilia,
2.arterial dissection,
3.paradoxical embolism,
4.and unusual arteriopathies
• In more than 60% of patients with ischemic stroke,
the cause is most often: atherosclerosis or heart
disease.

17. Further progress.
• Repeat CT of the head, performed 24 hours after the
administration of t-PA, revealed no evidence of hemorrhage,
and prophylactic enoxaparin(LMWH) therapy for deep
venous thrombosis was begun.
• Color Doppler echocardiography with the injection of an
agitated-saline contrast agent revealed evidence of a patent
foramen ovale(PFO) with right-to-left shunting.
• The d-dimer level was 5139 ng per milliliter (normal value,
<500).
• 2DECHO s/o an estimated right ventricular systolic pressure of
27 mm Hg, no RA/RV dilatation, and trace insufficiency of the
aortic, mitral, tricuspid, and pulmonary valves. EF 60 %,no
RWMA.

18. Further progress.
• venous duplex ultrasonography of both the legs
showed no evidence of deep venous thrombosis.
(The sensitivity of venous duplex ultrasonography is 94% and the specificity is 98% when patients
have symptoms and signs of deep venous thrombosis, However, the use of same as a screening
test in asymptomatic patients who are at risk for deep venous thrombosis has only 60%
sensitivity.)
• ventilation– perfusion scanning of the lungs
:perfusion defects in the right upper lobe and
bilateral lower lobes, as well as normal pulmonary
distribution of the tracer on ventilation imaging.
• CT pulmonary angiography revealed filling defects in
multiple branches of the pulmonary artery a finding
that confirms the presence of pulmonary embolism.

19. Additional Imaging
Studies.
A CT angiogram of the chest (Panel A) shows a
filling defect consistent with embolism in a
branch of the left pulmonary artery (arrow).
A pelvic magnetic resonance angiogram (Panel
B) shows the anatomical feature indicative of
the May-Thurner syndrome: severe stenosis of
the left common iliac vein (arrow) caused by
an overlying right common iliac artery.
An abdominal CT scan (Panel C) shows a mass
measuring 7.5 cm in greatest dimension
(arrow), a finding consistent with a renal-cell
carcinoma involving the right kidney.

20. Further search for cause of Pulmonary embolism
• Pelvic MR angiography revealed the anatomical
features indicative of the May–Thurner
syndrome: severe stenosis (>50%) of the left
common iliac vein caused by an overlying right
common iliac artery as well as collateral venous
drainage that suggests that the stenosis is
hemodynamically significant.
• The study also revealed a mass in the right kidney.

21. May–Thurner syndrome
• May–Thurner syndrome, a common anatomical anomaly
in which
• the right common iliac artery, a muscular structure,
extrinsically compresses the thin-walled left common
iliac vein. identified in up to 25% of an asymptomatic
population.
• For patients with ischemic stroke and patent foramen
ovale and without definitive evidence of deep venous
thrombosis, guidelines indicate that the current data are
insufficient to establish whether anticoagulation is
equivalent or superior to aspirin for the prevention of
recurrent stroke.
• Available data do not support a benefit of patent
foramen ovale closure.

22. Renal mass workup
• Abdominal CT confirmed the presence of an
enhancing, partially necrotic mass (measuring 7.5 cm
in greatest dimension), a finding consistent with a
renal-cell carcinoma involving the right kidney
• There are two major reasons that this patient would
have had deep venous thrombosis and stroke:
prolonged air travel and possible patent foramen
ovale with paradoxical embolism likely originated
from right kidney (RCC)

23. Post anticoagulation
• On the sixth hospital day, only 2 days after
anticoagulation was begun,
• the patient’s condition suddenly worsened. Aphasia
recurred,
• MRI revealed hemorrhagic transformation in the left
temporal lobe. Anticoagulation was immediately
stopped.
• When anticoagulation is contraindicated, because of an
increased risk of intracranial or systemic hemorrhage,
then placement of an inferior vena cava filter is a
reasonable option.

24. Nephrectomy Specimen.:a well-
circumscribed, yellow-orange mass,
measuring 7.0 cm in greatest dimension,
with central degeneration in the inferior
pole of the kidney.
(Panel B) shows nests of cells with clear
cytoplasm and prominent vascularity.
At higher magnification (Panel C) all
features s/o clear-cell renal-cell carcinoma
(Panel D) also shows extension of the
tumor into a muscle-containing segmental
branch of the renal vein; this finding is
confirmed on Masson trichrome staining to
detect collagen (blue) and smooth muscle
(red) (Panel E)
Immunoperoxidase staining for CD31 to
detect endothelial cells (Panel F).

25. Ultimate decision taken
• cardiac catheterization with patent foramen ovale
closure and placement of an IVC filter was performed
on the evening of the 6th hospital day.
• Six days later, right nephrectomy was performed.
• Later on developed established DVT with with
occlusion of the left common iliac vein, which
required two thrombectomies and ultimately
stenting to maintain venous patency of the left leg.

26. Thrombophilia workup
Parameters Results
PT,aPTT,AT-III normal
Lupus anticoagulant, normal
prothrobin gene mutation normal
Activated Protein C levels,Protein S normal

27. Final Diagnosis :
• On follow-up…
• The patient had no recurrent thrombotic events,
• has returned to work full-time and
• has resumed almost all her previous activities,
• although she has some difficulty with arithmetic and
executive functions
Acute ischemic stroke in Rt MCA territory ,causing
left hemiplegia , caused by paradoxical embolism
through a patent foramen ovale, in a patient with
the May–Thurner syndrome and a hypercoagulable
state due to an occult renal-cell carcinoma.

28. ADVICE:
If you hear hoof beats,
think of horses
But
if the pattern of hoof
prints appears
suspicious,
be on the lookout for a
zebra…

30. Stroke-WHO definition
A neurological deficit of
• Sudden onset,
• With focal rather than global
dysfunction,
• In which after adequate investigations,
symptoms are presumed to be non
traumatic vascular origin.
• Lasting for more than 24 hours.

31. Stroke-Epidemiology
• Third M/C cause of death after Malignancy
and Ischemic heart disease.
• M/C cause of Severe physical disability.
• Prevalence:1.54/1000 people.
• Death: 0.6 per 1000.
• Incidence and prevalence is on rise due to
defective life style .

32. Pathophysiology
• Blood flow autoregulated
• If blood flow-
1. Zero-Brain tissue death within 4-10 minutes
2. <16-18 ml/100g tissue/min-infarction within 1
hour
• Development of ischemic core and ischemic
penumbra
• Tissue surrounding core region of infarction is
reversibly dysfunctional
• Maintained by collaterels
• Can be salvaged if reperfused in time
• This is the primary goal of interventions

33. ischemic core and ischemic penumbra
<3 HOURS 6 HOURS AT 24 HOURS

34. Pathophysiology

35. Types of strokes.
Ischemic(85%) Hemorrhagic(15%)

36. Risk factors..
modifiable
• Hypertension
• Heart disease(AF,SABE)
• Diabetes mellitus
• Hyperlipidemia
• Smoking ,excess alcohol
• Oral contraceptives
• Elevated Homocystiene
• Pregnancy,migraine
• Obesity,sleep apnea
• Carotid stenosis
Non modifiable
• Age
• Gender(M>F)
• Race(afro-
caribbean>asian>european)
• Heredity
• Previous vascular event
• Coagulation disorder
• Cardiac disease

37. Ischemic stroke
Thrombotic
• Lacunar strokes
• Large vessel thrombosis
• Hypercoagulation disorders
Embolic
• Artery to artery
Carotid bifurcation
Aortic arch
• Cardioembolic
AF
MI
Mural thrombus
SABE
MS
Pradoxical embolus

38. Ischemic stroke
• 85% of strokes
• Arterial occlusion of intracranial vessels leads to hypo
perfusion
• Types-
1.thrombotic
2.embolic

39. Thrombotic stroke
• Atherosclerosis is MC pathology
• Hypercoagulation disorder-uncommon cause
1.Antiphospholipid antibody
2.Sickle cell anemia
3.Polycythemia vera
4.Homocystinemia
• Vasculitis: PAN,Wegener’s ,Giant cell arteritis

40. Thrombotic stroke.
• Lacunar stroke
• Accounts for 20% of all strokes
• Results from occlusion of deep penetrating arteries
• Clinically presented as lacunar syndrome
• Pathology: lipohylinosis and microatheroma
• Thrombosis leads to small infarcts called as lacunae

41. Thrombotic stroke.
• Lacunar stroke
• Accounts for 20% of all strokes
• Results from occlusion of deep penetrating arteries
• Clinically presented as lacunar syndrome
• Pathology: lipohylinosis and microatheroma
• Thrombosis leads to small infarcts called as lacunae

42. Embolic stroke.
1) Cardio embolic stroke
• embolus from heart gets lodged in intracranial vessels
• MCA gets M/C involved
• AF is M/C pathology
• Others: MI, Prosthetic valves, RVHD,SABE
2) Artery to artery
• Thrombus formed on atherosclerotic plaques gets
embolised to intracranial vessels
• Carotid bifurcation thrombosis is M/C pathology
• Others: aortic arch, vertebral artery

43. Circulation of brain

44. Anterior cerebral artery.

45. Middle cerebral artery.

46. Posterior cerebral artery.

47. Lacunar stroke.

48. Act FAST at the first sign of stroke!

49. Stroke:Differentials

50. NIHSS score: The National Institutes of Health Stroke Scale, or NIH Stroke
Scale (NIHSS) is a tool used by healthcare providers to objectively quantify the
impairment caused by stroke.

51. NIHSS and Patient Outcomes
• Total scores range from 0-42 with higher values representing
more severe infarcts
– >25 Very severe neurological impairment
– 15-24 Severe impairment
– 5-14 Moderately severe impairment
– <5 Mild impairment
(Adams, HP, et al. (1999). Neurology: 53: 126-131.)
• A 2-point (or greater) increase on the NIHSS administered serially
indicates stroke progression. It is advisable to report this increase.

52. NIHSS and Patient Outcomes
 Initial score of 7 was found to be important cut-off point
 NIHSS >7 demonstrated a worsening rate of 65.9%.
 NIHSS <7 demonstrated a worsening rate of 14.8% and were almost
twice (1.9x) as likely to be functionally normal at 48 hours (45%).
(DeGraba et al.,1999)
 NIHSS <5 most strongly associated with D/C home
 NIHSS 6-13 most strongly associated with D/C to rehab
 NIHSS >13 most strongly associated with D/C to nursing facility
(Schlegel et al., 2003)
 Likelihood of intracranial hemorrhage:
 NIHSS > 20 = 17% likelihood
 NIHSS < 20 = 3% likelihood
(Adams et al., 2003)

53. Adult suspected stroke algorithm

55. Critical time limits –from hospital arrival
• Immediate general assessment-10 minutes
• Immediate neurological assessment- 25 minutes
• Acquisition of CT scan brain-25 minutes
• Interpretation of CT scan- 45 minutes
• Administration of Fibrinolytic therapy- 60 minutes
from ED arrival
• Administration of Fibrinolytic therapy- 3 hours or 4.5
hours ,timed from onset of symptoms
• Admission to monitored bed -3 hours

56. diagnosis

66. Criteria for thrombolysis with rTPA (within 3
hours of symptom onset)
Inclusion:
• Diagnosis of ischemic stroke causing measurable
neurodeficit
• Onset of symptoms: <3 hours(4.5 in some selected ptients)
• Age >18 years
Exclusion:
Historical-
• Stroke, head trauma in last 3 months
• Previous IC bleed
• IC neoplasm/AVM/ Aneurysm
• Recent intracranial /intraspinal surgery
• Arterial line puncture at non compressible site in last 7 days

67. Criteria for thrombolysis with tPA (within 3 hours of
symptom onset)
Exclusion :
Clinical
• Signs and symptoms s/o SAH
• Raised BP > 180/110 mmhg
• BSL <50 mg/dl
• Active bleeding diathesis
• Active IC bleed
Hematological
• Platelet count:<1,00,000/cmm.
• Current anticoagulation use, INR >1.7,PT >15 sec, heparin within last
48 hours
• Current use of Direct thrombin inhibitors
Radiological
• CT demonstrates multilobar infarct (> 1/3 cerebral hemisphere
involved.)

68. Criteria for thrombolysis with tPA(from 3 to 4.5
hours)
Inclusion:
• same as before
Relative Exclusion:
• Age >80 years
• Severe stroke(NIHSS>25)
• OAC use irrespective of INR status
• H/O DM and previous ischemic stroke
• Wakeup stokes
• RISS(rapidly improving stroke symptoms)
(acc to ECASS-3 trial)

69. IV Alteplase
• IV Alteplase is 10 times more likely to help than other
measures
• Can cause bleeding in 1 out of every 1000 patient
• In some patients may cause fatal cerberal bleeding
• In menstruation- it may or may not cause pv bleeding
(IN CASE OF MI and lysis- heavy pv bleeding reported after
thrombolysis with alteplase)
• Informed written consent mandatory
• Max dose : 90 mg
• Strict BP control before lysis: use Nicardipine,labetolol
,Enalprilat etc
• Avoid excessive drop in BP (not more than 15% of initial BP) it
may increase ischemic penumbra by decrease in cerebral
blood flow.

73. Factor affecting recanalisation after tPA
• Size and site of clot
• Hematocrit
• Vessel involved
• Clot age andd composition(red cells+fibrin)

74. Hyperglycemia in stroke
• Hyperglycemia detrimental by producing anerobic
glycolysis and rise in tissue acidosis
• Increase free radical production
• Increase blood brain barrier permeability
• Persistent BSL >140 mg for first 24 hrs of stroke-poor
outcome
• AHA/ASA recommends insulin administration if BSL
>140 mg/dl.

75. Mechanical thrombectomy
• the most recent trial -SWIFT-PRIME, was presented at a
International Stroke Conference in Nashville on February 11,
2015
• Almost 50% of patients treated with tPA alone in the National
Institutes of Neurologic Disorders and Stroke (NINDS) trial had
achieved essentially full recovery However, subgroup analyses
of the NINDS data showed that patients with severe strokes
had only an 8% likelihood of achieving clinically significant
improvement with tPA.
• The poor outcome in these patients has inspired the search
for acute-stroke treatments that are more effective than tPA.

76. Mechanical thrombectomy
• Newer trials Has shown significant benefits in confirmed
large vessel occlusion.
MR CLEAN, REVASCAT
EXTEND-IA, EXTEND-4,
ESCAPE, and SWIFT PRIME,
• Mechanical thrombectomy better suits in proximal lesions
,anterior ciculation which are less likely to get opened in iv
thrombolysis.
• Best benefits seen in elderly population(>80).
• Applied within 6 hours of stroke onset
• Best results with second to third generation devices
• Requires NIHSS atleast >2/ASPECT >6
• >18 years of age without coagulation abnormaliites

80. MERCI retriever

81. Solitaire device

86. Secondary stroke prevention
Achieved by antiplatelet agents
1.Aspirin-
• 25% RR reduction of fatal stroke compared to
placebo (ATC trial,2002)
• 50-100 mg /day recommended (ESPS-2 /DUTCH-TIA
trail) as less GI bleed seen with similar efficacy as
325/day
2.Clopidogrel-
• No clear benefits, can be tried if intolerant to Aspirin
• Only decrease GI bleeding risk as compared to
Aspirin

87. Secondary stroke prevention
3.Aspirin+Clopidogrel (CHANCE Trial)
• No clear benefits
• More benefits in ACS
• More IC ,GI bleeding rates
4.ASA 25 mg +Dipyridamole 200mg (ESPS-2 trial)
• higher benefits than dipydamole or ASA alone
• Practically does not cause angina/MI
5.Cilstazol
• Good antiplatelet function
• But more side effect profile and less tolerated
• Less IC bleed as compared to Aspirin
6.Trifluzal (TACIP study)
• failed to show significantly superior efficacy of triflusal over aspirin
• associated with a significantly lower rate of hemorrhagic complications.

88. Next presentation ….
Next week presentation on the same
topic-
1-Localization of stroke.
2-different Stroke syndromes.