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Modern advances in the management of stroke

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Modern advances in the management of stroke Powered By Docstoc
					Modern advances in the
management of stroke
        Dr Neil Baldwin,
 Consultant Physician in General
     and Stroke Medicine,
    North Bristol NHS Trust
    neil.baldwin@north-bristol.swest.nhs.uk
                   Agenda
•   Drivers for change in stroke care
•   Recent advances in primary prevention
•   Recent advances in TIA
•   Recent changes in Acute Stroke care
    – Ischaemic stroke
    – Intracerebral haemorrhage
 What have been the drivers for the
recent development of stroke care?
http://www.rcp.london.ac.uk
            NSF:- Milestones
• April 2002 Every DGH which cares for stroke will
  have plans to introduce a specialist stroke
  service by 2004
• April 2003 Every DGH which cares for stroke will
  have established clinical audit systems to ensure
  delivery of RCP guidelines
• April 2004 PCG/T’s will have ensured that
  – Every practice uses protocols agreed with local
    specialist services can identify and treat patients at
    risk of stoke because of BP, AF or other factor
  – Agreed protocol for rapid referral and management of
    TIA
Using the National Sentinel Audit
                 Time to Admission to Stroke Unit

                      1600


                      1400   1481


                      1200
 N of patients




                      1000


                      800


                      600

                                     518
                      400


                      200                     280
                                                        171
                        0                                         111
                             0-5    5 - 10   10 - 15   15 - 20   20 - 25   25 - 30   30 - 35   35 - 40


                               Delay (day s) f rom stroke to admission to stroke unit
  Comparing Stroke Care 1999-2004

            1999   2002   2004

Stroke Unit 37%    73%    79%

median             20     20
no.beds
CT within   51     57     90
24 hours
           Primary Prevention
• Mass population
• High risk approach
  – Hypertension
  – Diabetes
  – CHD / PVD
  – Atrial fibrillation
  – Smoking
  – Alcohol
Primary prevention
   hypertension
                       Relative Risk for Stroke
                                                       Odds ratios and
                                                    95% confidence intervals


           Veterans Administration, 1967
           Veterans Administration, 1970
           Hypertension Stroke Study, 1974
           USPHS Study, 1977
           EWPHE Study, 1985

           Coope and Warrender, 1986

           SHEP Study, 1991

           STOP-Hypertension Study, 1991

           MRC Study, 1992
           Syst-Eur Study, 1997
                                                        0.63
                                                   (0.55 to 0.72)
           Total                               0                                       2
                                                       0.5          1       1.5

                                               Active treatment          Active treatment
He J, et al. Am Heart J. 1999; 138:211-219.   better than placebo       worse than placebo
Are any antihypertensives better?
LIFE: Blood Pressure Follow-up mean 4.8 y
       180
                         Atenolol
       160               Losartan
                                                  Atenolol 145.4 mmHg
                    Systolic
       140                                        Losartan 144.1 mmHg
mmHg




       120

       100           Mean Arterial
                                                  Losartan 81.3 mmHg

       80           Diastolic
                                                  Atenolol 80.9 mmHg


       60

       40
            0   6   12     18     24   30   36   42   48    54
                                Study Month
                                                  LIFE: Fatal/Non-fatal Stroke
                                              8                 Intention-to-Treat
Proportion of patients with first event (%)



                                              7                                     Atenolol

                                              6

                                              5
                                                                                                     Losartan
                                              4

                                              3

                                              2

                                              1                     Adjusted Risk Reduction 24·9%, p=0·001
                                                                    Unadjusted Risk Reduction 25·8%, p=0.0006
                                              0
                                                  0   6   12   18    24   30   36   42   48   54   60    66
                                                                          Study Month
                             Eprosartan
                       cerebrovascular events
             160
                              Eprosartan     Nitrendipine
             140

             120
Events (n)




             100

             80

             60
                                                  Risk reduction with
             40                                 eprosartan: 25% (P=0.02)
             20

              0
                   0    200    400     600    800     1000   1200   1400   1600

                                             Days
Transient Ischaemic Attack
     Definition of Stroke & TIA
• Stroke
  – A syndrome of rapidly developing clinical signs of
    focal (or Global ) disturbance of cerebral function,
    with symptoms lasting 24 hours or longer or leading
    to death. With no apparent cause other than of
    vascular origin.
• TIA
  – TIA is as above but lasting less than 24 hours


• Hatona 1976
        New definition of TIA
• A brief episode of neurological dysfunction
  caused by focal brain or retinal ischaemia
  with clinical symptoms lasting less than
  one hour without evidence of infarction
 Risk of recurrent stroke after TIA and minor stroke




Coull et al BMJ 2004
                 TIA Clinic

                  1%
                 1%
           8%

      8%                      TIA
                              Possible TIA
                              Syncope
12%
                        48%   Funny turn
                              Epilepsy
                              Vertigo
 11%                          Hyoglcaemia
                              brain tumour
           11%
  CT scanning in TIA is only worth doing
   if it in within one week of the clinical
                     event




Wardlow 2004
Secondary prevention of stroke & TIA


• For patients with TIA
 Hypertension / Blood pressure
 Ant platelet therapy
 Statins
 Carotid Endarterectomy for patients with
  symptomatic carotid stenosis
 Anticoagulant therapy for patients with atrial
  fibrillation
 Smoking
          Effect of Aspirin and Clopidogrel
                     Match Trial




The lancet 2004 Vol. 364, 9431; pg. 331
          Carotid Artery Stenosis



  External Carotid


                             Stenosis at
                             bifurcation of
                             Internal Carotid



Common Carotid
High Grade Carotid Stenosis
       Carotid Endarterectomy

• European carotid trialists collaborative group
• European Carotid Surgery Trial (ECST)
• North American symptomatic carotid endarterectomy trial I &
  II(NASCET)


• 3 RCT’s (symptomatic) – 6143 pts

• Severe Stenosis                  RRR 48% NNT 15
        Efficacy of Carotid endarterectomy for
        symptomatic stenosis
  30

  25

  20

% 15                                           Surgery
                                               Control
  10

   5

   0
       ECST 70-99%   ECST 82-99 NASCET 70-99
     Asymptomatic Carotid Artery Stenosis




The Lancet. 2004. Vol. 363, 1491,
The Lancet. 2004. Vol. 363, 1491,
Internal carotid artery (ICA) origin angioplasty
          Carotid Angioplasty
• Carotid Endarterectomy is the gold standard for
  Symptomatic and asympttomatic carotid
  stenosis
• CAS has an expanding role for
  revascularization, particularly in high-risk
  patients.
• Several randomized prospective trials are
  ongoing to better define the indications for CAS
Causes of Ischaemic Stroke
Cause of TIA and Cerebral infarction
• Embolus                 • Thrombosis
• Carotid atheroma        • Abnormality of vessels
                             –   Atherosclerosis
• Cardiac                    –   Autiimmune disease
  – Atrial fibrillation      –   Vasculitis
  – Mural thrombus           –   Wall dissection
  – Patent foramen        • Abnormal clotting
    Ovale                    –   Polycythemia
                             –   Thrombocythemia
                             –   Hyperviscosity
                             –   Clotting disorders
                                  • Inherited
                                  • acquired
                          • Migraine?
 Cause of TIA and Cerebral Infarction
• Embolus                 • Thrombosis
• Carotid atheroma        • Abnormality of vessels
                             –   Atherosclerosis
• Cardiac                    –   Autiimmune disease
  – Atrial fibrillation      –   Vasculitis
  – Mural thrombus           –   Wall dissection
  – Patent foramen        • Abnormal clotting
                             –   Polycythemia
    Ovale
                             –   Thrombocythemia
                             –   Hyperviscosity
                             –   Clotting disorders
                                  • Inherited
                                  • acquired
                          • Migraine?
       Patent Foramen Ovale
• A PFO is the persistence of a hole (the foramen
  Ovale) in the septum between the right atrium
  and the left atrium of the heart.
  – Prenatally it allows blood to bypass the lungs and go
    straight to the left side of the circulation.
  – FO usually closes spontaneously after birth but
  – In as many as 25% of the population it does not close
    properly after birth and remains patent throughout life
  – The presence of a PFO is more common in patients
    with Migraine and Aura
 Patent Foramen Ovale and Stroke
• In most people the PFO causes no
  complications.
• There is however an association between PFO
  and Cerebral Embolic Stroke.
• The mechanism is believed to be that thrombus
  from the venous circulation can pass into the
  arteries through the PFO and then embolise to
  the brain.
• The risk of Ischaemic stroke is increased in the
  presence of Atrial septal aneurysms
Transthoracic Echocardiograph of PFO
Transthoracic Echocardiograph of PFO
High-risk features in patients with PFO
• Valsalva inducing manoeuvres and stroke
• Coexisting hypercoagulable state
• Recurrent strokes
• PFO with large opening, large right-to-left shunt,
  or right-to-left shunting at rest
• Coexisting atrial septal aneurysm) should
  prompt PFO closure.



    Arch Intern Med. 2004;164:950-956
     Treatment of Patent Foramen
          Ovale and Stroke
• Patients with PFO as an isolated finding no treatment is
  required
• Patients who have had an embolic event treatment
  includes
   – Antithrombotic
      • Aspirin)
   – Anticoagulation
      • Warfarin
   – Surgical closure
      • Open heart
      • Percutaneous Closure device
• there remains a lack of consensus regarding the optimal
  management strategy
            Drug induced Stroke
• Hormone Replacement
  Therapy
• Oral Contraceptive Pill
• Cox 2 Inhibitors

• Atypical Neuroleptic agents
Strategies for preventing stroke and
      reducing stroke disability

  blood pressure                                                         stroke mortality
  smoking
  lipids
                       mass popl.
                       strategy                        acute treatment

                                        First stroke            Secondary              recurrent
                                                                prevention             stroke

                   high risk strategy
                                                       Rehabilitation

      hypertension
      TIA                                                                     Stroke related
      Atrial fibrillation                                                     disability
      other vascular disease
             Immediate Care
• All patients who may have a stroke will
  require admission to hospital and should
  be treated by a specialist stroke team in
  a designated stroke unit including a
  physician specialising in stroke medicine




National service framework
Are stroke units worthwhile?
                                     Incremental Costs(US$/PPP)




                                             1000
                                             2000
                                             3000
                                             4000
                                             5000
                                             6000
                                             7000
                                             8000
                                             9000




                                                0
                     Kaunas A(Lithuania)

                     Kaunas B (Lithuania)

                         Menorca (Spain)

                        Warsaw (Poland)

                         Kuopia (Finland)

                        Almada (Portugal)




Incremental cost
                          Florence (Italy)

                           Dijon (France)

                        Turku B (Finland)
Hazard Ratio
                            London (UK)
                                                                                               CI) by centre (Riga (Latvia) as reference )




                        Turka A (Finland)

                   Copenhagen (Denmark)
                                             0
                                                                         1




                                                 0.2
                                                       0.4
                                                             0.6
                                                                   0.8
                                                                             1.2




                                                  Hazard Ratio
                                                                                   Adjusted incremental costs (US$/PPP) and hazard ratios (with 95%
      Acute treatment of Stroke
•   Accurate diagnosis of stroke
•   Definition of stroke type
•   Acute general medical care
•   Re-perfusion
•   Neuroprotection
       Stroke: Differential Diagnosis


• Syncope                  • Subarachnoid
• Partial epileptic          haemorrhage
  seizure with Todd’s      • Neuroinfection
  paresis                  • Neoplasm
• Migraine attack (aura)   • Brain injury
• Hypoglycaemia            • Multiple sclerosis
• Hysteria                 • Peripheral vertigo
• Intoxication
      Acute treatment of Stroke
•   Accurate diagnosis of stroke
•   Definition of stroke type
•   Acute general medical care
•   Re-perfusion
•   Neuroprotection
Computed tomography scan showing a large left putamen
hemorrhage (A)
Cerebral infarction


         Brain swelling



         Focal cortical effacement




         ventricular compression
Atherosclerotic plaque locations in anterior circulation
Carotid dissection
Unenhanced computed tomography from 69-year-old woman
  presenting brain hemorrhages due Amyloid Angiopathy
Hemispheric arteriovenous malformation
Cavernous malformations
      Acute treatment of Stroke
•   Accurate diagnosis of stroke
•   Definition of stroke type
•   Acute general medical care
•   Re-perfusion
•   Neuroprotection
Specific General Measures for acute stroke
• Hyperglycaemia
  – is a frequent finding in acute stroke
      • Diabetes
      • Stress hyperglycaemia
  – Raised blood glucose is positively associated with greater
    mortality and poor functional outcome
  – Intervention studies in acute MI suggest tight glucose control
    improves outcome.
• Temperature regulation
  – Body temperature on admission predicts both the severity and
    long term outcome
  – 10C rise independently predicts a 30% relative increase in long
    term morbidity or death.
  – Trials of paracetamol and sponging are inconsistent
                   Mortality and Dysphagia

                                safe
                                not safe
                           45
                           40
                           35
                           30
                           25
                         %
                           20
                           15
                           10
                            5
                            0


stroke 1996;27:1200-04
Specific medical therapy
      Acute treatment of Stroke
•   Accurate diagnosis of stroke
•   Definition of stroke type
•   Acute general medical care
•   Re-perfusion
•   Neuroprotection
Acute Stroke thrombolysis
Pathogenesis of Ischaemic stroke




      Penumbra
                 Infarction
        Randomised trials of rt-PA given within 3 hours of Acute
                          Ischaemic Stroke
            Outcome: Death or Dependency (Rankin  3)



STUDY                             ODDS       RATIO


ECASS


ECASS II


NINDS


TOTAL (95% CI)                                 0.55 (0.42 - 0.72)

                        1        2       1            5        10
                       Favours Treatment             Favours Control
                                                        Cochrane 1999
Risk of death dependency and good functional
 outcome in randomised trials of rt-PA given
         within 3 hours of acute stroke

                                             Alive and independant
                                             alive but dependant
                                             Dead
 100%

 80%                            30.2
           44.3
 60%

 40%                            51.4
           36.4
 20%
           17.3                 18.4
  0%
        Thrombolysis          Control


                   Cochrane September 1999
  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)

 4.0

 3.5
                  <3h                         3-4 h                        > 4,5h
 3.0              SITS-MOST                  uncetain
                                                              except selected patients
 2.5

 2.0

 1.5

 1.0

 0.5

 0.0
       60    90      120      150      180       210       240       270     300    330     360

                              Stroke onset to treatment time (OTT) [min]



Brott TG. International Stroke Conference 2002; abstract.
Hyperdense middle cerebral
         artery



                Hyperdense middle cerebral
                artery
Early Hypodensity



           Hypodensity
  Better Patient Selection by Dynamic MRI?

Case 1: 2.5 hours after onset, NIHSS 15




     MRI                 DWI              PWI
Better Patient Selection by Dynamic MRI?
Case 1: at 24 h, NIHSS 5




      MRI                  DWI    PWI
    Intra arterial Thrombolysis
• PROACT II
  – Intra arterial Prourokinase
  – 6 Hour time window
  – Relative risk reduction of 15% in functional
    outcome
  – No difference in mortality
  – Procedural complication 9%
  – Early Intra cerebral haemorrhage 10%
    Mechanical clot removal in acute stroke
                 MERCI trial
       • Phase 1 Trial
• Cerebral embolectomy
  successful recanalisation in 69
  /141 (48%)
• In combination with rtPA in 17
  cases
• Procedural complications 7.1%
• Could extend the time window
  to 8 hours
    What are the current delays to treatment?

•   Patient awareness
•   GP awareness
•   Hospital admission protocols
•   Medical staff
•   Others
                                                                                         Section 1 Slide30




Onset to Entry (By referral method)
               70



               60



               50


                                                                                                 999
  Pt Numbers




               40
                                                                                                 GP
                                                                                                 Other
               30                                                                                GP+999


               20



               10



               0
                    0-<1   1-<2   2-<3   3-<4   4-<5   5-<6   6-<9   9-<12   12-<24   >=24
                                                   Hours

ASIST data 1999
  Pre of hospital recognition TIA
              FAST
• Facial Weakness                   • Stroke Association campaign
   – Can person smile                 to raise awareness
   – Has mouth dropped              • Practice staff should be trained
                                      to inform doctor immediately if
• Arm Weakness                        patient calls with symptoms
   – Can person raise both arms       identifiable
• Speech problems                   • Ambulance crews now trained
   – Can person speak clearly and     to use FAST score to prioritise
     understand what you say          Calls and dispatch
• Test all three symptoms           • Act FAST call 999
 Stroke Treatment 2004 and Beyond
                 Stroke onset            Call
 Secondary
 prevention                           emergency
                                       services
 Full recovery                               Activated
                                            (15 minutes)




Thrombolysis
   Drugs

                                A+E stroke team
                   Brain scan
Acute Management of Cerebral
        haemorrhage
       Acute Management of Cerebral
               haemorrhage
   • Acute treatment        • Secondary Prevention
• Conservative              • Antihypertensive
• Surgical                    Treatment
  – STITCH trial
  – Shunt for
    hydrocephalus
• Medical Therapy
  – Recominant Factor VII
 Early surgery versus initial conservative treatment in patients with
    spontaneous supratentorial intracerebral haematomas in the
 International Surgical Trial in Intracerebral Haemorrhage (STICH):
                         a randomised trial




The Lancet 2005. 365, 387,
The Lancet 2005. 365, 387,
Recombinant Factor VIIa
            • Mortality 29% in
              placebo group, 18%
              in all 3 treatment
              groups.
            • Mortality reduced by
              35% in each rFVIIa
              group (p=0.02).
            • Dose-response effect.
Recombinant Factor VIIa
      Acute treatment of Stroke
•   Accurate diagnosis of stroke
•   Definition of stroke type
•   Acute general medical care
•   Re-perfusion
•   Neuroprotection
          Primary outcome mRS
                  p=0.038 favours NKY059



NKY059    15.4    18   11.4 14.2 16.9     24          0
                                                      1
                                                      2
                                                      3
                                                      4
placebo   11     20    11.7 12.7 20.6     24          5&death




      0%         20%   40%    60%       80%    100%
     Per protocol outcome mRS
               p=0.028 favours NKY059



NKY059   15.4 18.5 11.3   20   17.6   23.6      0
                                                1
                                                2
                                                3
                                                4
placebo 10.5 20.3 12.2 12.5 20.5      23.7      5&death




      0%     20%   40%     60%     80%   100%
                Summary 1
• There is good evidence for
  – General medical care in acute stroke
  – Acute Aspirin treatment
  – rtPA thrombolysis for acute stroke < 3 hrs
  – Acute and rehabilitation on a specialist stroke
    unit
                 Summary 2
• Transient Ischaemic Attack is
  – A strong predictor of acute stroke
  – Often under diagnosed
  – Often misdiagnosed
  – Effective secondary prevention has been established
  – Early secondary prevention is needed as recurrence
    tends to occur early
  – Current definition is no longer appropriate
Thank you

				
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