Stroke thrombolysis: Benefits and pitfalls

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Stroke thrombolysis Benefits and pitfalls

• Dr Neil Baldwin
• Consultant Physician North Bristol NHS Trust
• Clinical lead AGW Stroke Network
• Clinical Lead Acute Stroke NHS Institute

2
Benefits of Stroke Thrombolysis

• Reduced mortality
• Reduced Disability
• Reduced need for institutional care
• Reduced LOS mean 12 days v 23 days

3
Intention to treat
4
Risks of Thrombolysis

• Intracerebral Haemorrhage
• Symptomatic
• Asymptomatic
• Extracranial Haemorrhage
• Anaphylaxis

5
Is thrombolysis safe and effective in practice?

• SITS-MOST
• ICH at 7 days
  7.3 in SITS-MOST vs 8.6 in RCTs
• 3 month mortality 11.3 in
  SITS-MOST vs 17.3 in RCTs
• Complete recovery at 3 months 38.9
  (SITS-MOST) vs 42.3 (RCTs)

Lancet Jan 2007
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Pitfalls of Thrombolysis

• Treatment of Stroke mimics
• Delayed treatment
• Not treating

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Stroke mimics
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Clinical Evaluation

• Five question approach
• Is it a Stroke?
• Which type of stroke?
• Where is the Stroke?
• What caused the Stroke?
• Will thrombolysis be helpful?

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Stroke mimics

• Subarachnoid haemorrhage
• Neuroinfection
• Neoplasm
• Brain injury
• Multiple sclerosis
• Peripheral vertigo

• Syncope
• Partial epileptic seizure with Todds paresis
• Migraine attack (aura)
• Hypoglycaemia
• Hysteria
• Intoxication

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Mr BD 68yr

• HPC T 13.45
• Sudden onset left hemiparesis
• Left visual field defect
• Dysarthria
• Risk Factors
• Hypertension on Atenolol
• Ex Smoker
• Past Medical History
• Nil else

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Mr BD 68yr

• General Exam
• Alert GCS 15
• Pulse 80 SR
• BP 175/85
• BM 5.6mmol/L
• Heart normal

• Neurological
• Normal commands
• L VII palsy mild
• L visual field defect
• L hemiparesis
• Dysarthria

NIHSS 15
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Mr BD 68yr

• Time line
• Onset T0 13.45
• ED Arrival 14.20
• CT scan 14.45
• Stroke team saw pt in Scanner room
• Thrombolysis 15.00
• Outcome
• Fully independent when reviewed 1730
• Repeat CT 24 hrs normal
• Carotid Doppler gt 75 Right ICA
• Discharged Following day with plan for
  Endarterectomy in 2 Weeks

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Benefit of rt-PA for Acute Stroke
mRS 0-1 at day 90 Adjusted odds ratio with 95
confidence interval by stroke onset to treatment
time (OTT)
lt 3 h SITS-MOST
3 - 4.5 h RCT ECASS III
gt 4,5h except selected patients
Adjusted odds ratio
Stroke onset to treatment time (OTT) min
Brott TG. International Stroke Conference 2002
abstract.
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Mr PB 72yr

• HPC T 14.20
• Word finding difficulty
• Mild right hemiparesis
• No visual field defect
• Risk Factors
• Hypertension on Atenolol Bendroflumethazide
• Smoker
• Cholesterol
• Past Medical History
• Previous MI

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Mr PB 72yr

• General Exam
• Alert GCS 15
• Pulse 80 SR
• BP 185/85
• BM 8.6mmol/L
• Heart clinically enlarged

• Neurological
• Normal commands
• Moderate expressive aphasia
• R VII palsy mild
• R visual field defect
• R hemiparesis mild

NIHSS 14
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Mr PB

• Time line
• Onset T0 14.20
• ED Arrival 15.30
• CT scan 1600
• Stroke team saw pt in ED soon afterwards
• Marked improvement in NIH 4
• No thrombolysis
• Outcome
• Fully independent when reviewed next day
• CT Carotid Angiogram gt 75 L ICA
• Discharged Following day with plan for
  Endarterectomy in 1 Weeks

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Mrs SS 45yrs

• HPC
• Sudden onset of L hemiplegia
• Drowsy
• Severe Dysarthria
• Risk Factors
• Hypertension

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Mrs SS 45yr

• General Exam
• Drowsy GCS 14
• Pulse 80 SR
• BP 165/85
• BM 5.6mmol/L
• Heart clinically enlarged

• Neurological
• Abnormal commands
• Severe Dysarthria
• L VII palsy severe
• L visual field defect
• L hemiplegia

NIHSS 22
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Mrs SS

• Blood sugar normal
• Blood Hb 7.9 g/dL
• MCV 76
• UE Normal

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Mrs SS 45yrs
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Mrs SS 45yrs
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Mrs SS

• Time line
• Onset T0 16.30
• ED Arrival 18.45
• CT scan 1900
• Stroke team saw pt in ED soon afterwards
• Discussion about menohhagia DW Gynae
• Thrombolysis given 2.45 hrs after onset
• Outcome
• when reviewed next day no change in NIHSS
• 3 days after admission sudden deterioration in
  condition GCS 7
• CT Repeat

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Mrs SS 45yrs
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Mrs SS 45yrs
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Mrs SS 45yrs

• Malignant Middle Cerebral Artery Ischaemic
  Syndrome
• Non dominant hemisphere
• Very High mortality
• Referred to Neurosurgeons
• Uncertainty about benefits of decompression
• Underwent hemi-craniotomy
• Died few days later

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Mrs SK 55yr

• HPC
• Sudden onset left hemiparesis
• Loss vision in Left eye
• Severe headache with mild photophobia
• Risk Factors
• No BP/ Cholesterol/ Diabetes / Vascular disease /
  Non Smoker / Ex HRT
• Past Medical History
• Hysterectomy 35 yr HRT for 5 yrs only
• Migraine since childhood

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Mrs SK 55yr

• General Exam
• Alert GCS 15
• Pulse 80 SR
• BP 140/75
• BM 4.6 mmol/L
• Heart normal

• Neurological
• Normal commands
• mild facial weakness
• Mild left hemiparesis
• Speech mild Dysarthria

NIHSS 10
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Mrs SK 55yr
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Mr SK

• Time line
• Onset T0 0850
• ED Arrival 1015
• CT scan 1045
• Stroke team saw pt in ED soon afterwards
• History of headache explored long history of
  classical migraine
• fortification spectra Scotoma
• GI Disturbance
• Hemicranial headache
• 1 previous episode of weakness
• Not Thrombolysed

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Mrs SK

• Subsequent investigations
• No evidence of atherosclerosis
• Bubble contrast ECHO confirmed a PFO
• Strong Relationship between PFO and Migraine
• Small increase in risk of Stroke

35
Mrs GW 72yr

• HPC
• Got up and was well
• After breakfast husband noticed a left facial
  weakness and Dysarthria
• Risk Factors
• Atrial Fibrillation / Hypertension
• PMH
• none

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Mrs GW 72yr

• General Exam
• Alert GCS 15
• Pulse 80 AF
• BP 112/75
• BM 4.6 mmol/L
• Heart enlarged

• Neurological
• Normal commands
• Mild L facial weakness
• Mild left hemiparesis
• Speech mild Dysarthria

NIHSS 11
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Mrs GW
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Mrs GW 72yr

• Seen in ED
• CT showed Chronic Subdural
• No History of Falls or Head Trauma
• Transfer to Neurosurgeons
• Good recovery 3 months later

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Mrs SB 52yr

• HPC
• Sudden onset of right hemiparesis
• Right visual loss
• Risk factors
• None
• Past medical history
• nil

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Mr SP 44yr carpenter

• HPC
• Monday 26th November 2007
• At work collapsed no recall of the prodrome he
  thought LOC 5 minutes
• On recovery right sided weakness
• Slurred speech
• Risk Factors
• Smoker 30 day / hypertension poor compliance
• Past Medical History
• Previous admission with blackout 2 yrs ago
• Social History
• Drinks 3-4 cans per day more at weekends

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Mr SP 44yr

• General Exam
• Tattoos
• Alert GCS 15
• Pulse 100 SR
• BP 112/75
• BM 4.6 mmol/L
• Heart normal

• Neurological
• Normal commands
• Mild R facial weakness
• Mild R hemiparesis
• Speech mild Dysarthria he said normal for him

NIHSS 11
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Mr SP
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Mr SP
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Mr SP

• Bloods
• Hb 11.5 g/dL MCV 99
• Bilirubin 29
• ALT 67
• Alk Phos normal

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Progress

• Reviewed in the ED
• Not thrombolysed as I felt likely to be due to a
  seizure
• Subsequent review of old noted previous admission
  thought to be a withdrawal seizure

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Mrs AS 75yr

• HPC
• Sudden onset of a left visual field defect whilst
  driving her car
• Managed to get home
• Daughter thought she had a left facial weakness
• Risk factors
• hypertension

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Mr AS 75yr

• General Exam
• Alert GCS 15
• Looks well
• Pulse 70 SR
• BP 132/75
• BM 4.6 mmol/L
• Heart normal

• Neurological
• Normal commands
• Mild L facial weakness
• No hemiparesis
• Speech mild Dysarthria

NIHSS 5
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Mrs AS 75yr
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Mrs AS 75yr
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Mrs AS 75yr
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Mrs AS

• Subsequent examination revealed a left Breast
  mass confirmed to be an Adenocarcinoma

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Mr BT 59yr

• 0950 Great Western Ambulance call patient in
  Malmsbury can we bring for thrombolysis
• 1105 Arrived in ED
• Sudden onset Right hemi paresis _at_ 0930
  according to Ambulance crew
• Found by wife in bedroom last seen just after
  0900

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Mr BT

• Risk factors
• Hypertension
• Arial Fibrillation
• Was on Warfarin until 6 weeks ago but stopped by
  GP as the patient was not happy on Warfarin.

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Mr BT

• General Exam
• GCS 14
• Pulse 85 AF
• BP 132/75
• BM 4.6 mmol/L
• Heart normal

• Neurological
• Not obeying commands
• R facial weakness
• R homonymous hemianopia
• R Hemiplegia
• Speech Aphasia

NIHSS 18
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120 minutes after symptom onset
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120 minutes after symptom onset
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120 minutes after symptom onset
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120 minutes after symptom onset
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CT Angiogram
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CT Angiogram
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CT Angiogram
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Mr BT

• Time line
• Onset T0 0900 - 0930
• ED Arrival 1105
• CT scan 1115
• Stroke team saw pt in CT room 1128
• Thrombolysis given 1140

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Mr BT

• 24 hr NIH score 11
• CT scan
• Discharges at day 8
• NIHSS 6

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24 hours post thrombolysis
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24 hours post thrombolysis
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Mr BT

• 24 hr NIH score 11
• CT scan
• Discharges at day 8
• NIHSS 6

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Mrs MO 62yr

• HPC
• Sudden onset of right hemiplegia
• Aphasia
• NIHSS22
• Risk factors AF Hypertension

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MA
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MA
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Mrs A

• Thrombolysed
• Marked improvement

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How may we improve diagnostic accuracy?

• The early diagnosis of acute stroke is difficult
  and relies on clinical experience
• Diagnostics can help with the exclusion of
  haemorrhage and alternative brain disorders
• The frequency of cases suitable for thrombolysis
  is at best 10 of all ischaemic stroke and at
  present in UK is used in lt0.2.
• Individual ED clinician experience will be low
• There are relatively few Stroke Consultants in
  the UK and 10 in AGW

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Conclusion

• Important steps are
• Is it a stroke/ be aware of stroke mimics?
• Is the stroke an infarct or haemorrhage CT is
  sensitive?
• If ischaemic stroke does the NIHSS fall within
  the selection range?
• lt 5 likely to recover without thrombolyis so no
  benefit from treatment except aphasia or
  hemianopia
• gt 25 very high risk of bleeding
• Is there another exclusion criteria
• Is there a significant improvement in NIHSS
• Can the thrombolysis treatment be given within
  4.5 hours ?

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Conclusion

• Give rt-PA if no Contra-indication
• More likely to do good than harm
• Transfer to Stroke unit
• Standardised observation
• Be aware of neurological deterioration
• Not all bleeding