1. QUALITY OF LIFE IN POST-STROKE PATIENTS -
ROLE OF NOOTORPIL
Prof. A.V. SRINIVASAN
29th June 2003
Madras Medical College, Chennai-3

2. STROKE
• Third cause of death after heart disease and
cancer
• Prevalence rates are around 500- 800 /
100,000
• Enormous economic consequences
A bad teacher complains;
A good teacher explains;
The best teacher inspires;

3. STROKE IN INDIA
• A huge base of population
• A prevalence rate of 900/ 100,000 can lead to an
epidemic of stroke
• 2% of all hospital admission, 4-5% of medical and
20% of neurological admission have CVD
• Incidence of stroke in younger persons (<40years)
is high (13-32%) as compared with western data
Science is below the mind; Spirituality is beyond the mind

4. Stroke - Risk factors
• The risk factors for CVD and CAD are the same
– hypertension
– diabetes mellitus
– stress
– smoking
• Crude prevalence rate for CVD in India is 90-222
per 100,000
Every thing should be made as simple as
possible; but not simpler

5. Stroke
• 85-90% of the total stroke are ischemic in
origin while hemorrhagic stroke constitute
only 10-15%
• Main causes of ischemic stroke
– thrombosis
• atherosclerosis
• vasculitis
• arterial dissection
• hematological disorders
• drug absue
– embolism
– vasoconstriction

6. Stroke synonyms
• Cerebrovascular
accidents
• Apoplexy
• Cerebrovascular
insufficiency
Speak obligingly even if you cannot oblige

7. Stroke pathology
• Disruption of blood supply to some
part/s of the brain
• Sudden onset of symptoms
(paralysis, aphasia, temporary
amnesia)
• Symptoms due to damage to
neurological functions / neurons
(neurological deficit)
Neuronal damage, including that of neuronal cell
membrane

8. Neuronal damages
types
Ischemic neuronal damage begins a few minutes
after disruption of the blood supply and not
immediately, and therefore it is known as post-
stroke sequel.
Damage can be of 2 types
• Zone of dead neurons - Core
• Zone of damaged neurons - penumbra

9. Ischemic Neuronal injury
• In the core region, failure of glucose and
oxygen delivery leads to rapid depletion of
energy stores and cell death
• Cells remain viable for several hours within
the penumbra region
Develop the heart; art comes automatically

10. Damage to the cells
(neurons) results in
defective
neurotransmission,
resulting in the clinical
manifestations of the
post-stroke sequlae

11. Clinical manifestation
• Abrupt onset of focal neurologic deficits
• manifestations can be in the form
– TIA (transient ischemic attack)
– RIND (reversible ischemic neurologic deficit)
– Completed stroke
– Progressing stroke / stroke in evolution
Symptoms vary depending on the location of
occlusion and the extent of the spared collateral
flow

12. Post-stroke sequelae symptoms
• Motor weakness
• Paralysis
– half side of the body (hemiplegia)
– complete body (paraplegia)
• Aphasia
• Memory loss

13. Management
• Recovery of neurological functions is the
key goal in the management
• Two ways of bringing about the above are
– pharmacotherapy
– rehabilitation
Knowledge without action is useless;
Action without knowledge is foolish

14. Pharmacotherapy
• Drugs acting inside the vessel
– Thrombolysis
– Anti-platelet agents
– Anti-coagulation therapy
• Drug acting on the neuronal level
– Nootropil
Let the wave of memory, the storm of desire, a fire of emotion
pass through without affecting your equanimity

15. Money comes and goes, morality comes and grows
Nootropil is approved for the
management and early recovery of
symptoms of post-stroke sequale of
thrombotic origin
Love is selfishness and selfishness is lovelessness

16. Neuronal salvage
• Collateral circulation tries
to take over from the
obstructed vessel to supply
blood to neurons
• Nootropil reaches the
damaged neurons through
these collateral circulation

17. Role of Nootropil
• Crosses the blood brain barrier and binds to the
neuronal cell membrane
• Basic action of the drug is on the cell membrane
specially that of the neurons
• Helps to limit the damage in the penumbra region
• Helps in the early recovery of neuronal function
• No drug interactions with Thrombolytics and anti-

18. • The action of Nootropil on the neuronal cell
membrane helps to improve its overall functioning

19. Nootropil
mechanism of action
• After binding to the neuronal cell membrane
– improves the membrane fluidity
– improves the uptake of glucose and oxygen in the
neurons, thereby reducing the effects of hypoxia
– improves the functioning of the receptors and
neurotransmitters
– improves intra-hemispheric transmission
Helps to limit neuronal damage, and early restoration of
neuronal function

20. Nootropil
other actions
• Nootropil also binds to the cell membranes
of
– RBC to improve its deformability resulting in
better oxygen supply
– Platelets to reduce hyper-aggregability
Teachers are reservoirs from which, through the process of
education, the students draw the water of life

21. Dose of Nootropil
• Initiate therapy with IV bolus (60ml, 200mg/ml)to
attain the desired levels through the collaterals
(this will prevent progression of damage)
• Follow-up with IV infusion for the next few days
• Maintain therapy with Oral Nootropil 4.8gms per
day for atleast 12 weeks for the optimum results
It is not your position that makes you happy or unhappy
It is your disposition

22. Injured Brain
25% men
1. 45 85 yrs - Stroke occurs
20% women
2. Guidelines for 24hrs: Mandatory
Level of Evidence
Level A: Based on RCT or Meta analy. of RCT
Level B: Based on Robust Experiment or
Observation Studies
Level C: Based on Expert opinion.
A good teacher is a perpetual learner

23. According to WHO
Doctor assessment of Handicap may not coincide with Patients
Assessment. Neurologist depends on physiotherapy, occupation
therapy and speech therapy in rehabilitating the stroke patients.

24. NEUROLOGIC PREDICTORS.
• Flaccid Paralysis for more than 96 hrs
• When tendon reflexes recover without return of voluntary
movement – prognosis poor
• Recovery of sensory less in usual to a degree. Postion
sense recovers but not pain and temperature
• Recovery from Dysphasia is never complete
• Dysarthria usual improves and Dysphagia never improves
• Diplopia due to brain stem is usually permanent
• Conjugate gaze – recovers
• Vertigo improves but hearing loss is permanent
• Pseudobulbar palsy permanent

25. 1. History And Examination
a. Stroke clerking Performa (1994) R.C.P.
1. Improved patient Assessment
2. Improved Management - not clear
3. Improved outcome - not clear
b. Examination
1. Secure Diag of Stroke
2. Specify Impairment
3. Identify sub type of Ischemic stroke
Learn to adapt, adjust and accommodate
Learn to give, not to take and learn to serve not to rule

26. Total anterior circulation syndromes :
Implies a large cortical stroke in middle cerebral or
middle and anterior cerebral artery territories. It is
charecterised by
• A combination of New higher cerebral dysfunction
and homonymous visual field defect and an
ipsilateral motor and/or sensory deficit involving at
least two out of three areas of the face, arm or leg
Hate screeches, fear squeals; conceits trumpets
but love since lullabies

27. Partial anterior circulation syndrome
• Implies a cortical stroke in middle or anterior
cerebral arterial territory.
• They are patients with two out of the three
components of the TACS or new higher
cerebral dysfunction alone or a motor/sensory
deficit more restricted than those classified as
a TACS.
Reputation is made in a moment; character is built in a life time

28. Lacunar syndrome
Implies a sub cortical stroke due to a small vessel
disease
• Pure motor stroke
• Pure sensory stroke
• Sensory motor stroke
• Ataxic hemiparesis
NB: Evidence of higher cortical dysfunction or
disturbance of consciousness excludes a lacunar
syndrome

29. Posterior circulation syndrome
• Ipsilateral cranial nerve palsy with
contralateral motor and or sensory deficit
• Bilateral motor and/or sensory deficit
• Disorder of conjugate eye movement
• Cerebellar dysfunction without ipsilateral
long tract involvement
• Isolated homonymous visual field defects
Character gets you out of bed commitment moves you to action
faith, hope and Discipline follow through to completion

30. Diagnostic evaluation of ischemic stroke
The diagnostic evaluation should include
parallel assessment of the following.
1. Imaging of the infarct
2. Vascular studies
3. Cardiac evaluation
4. Hematologic and other blood testing
It is the providence of the knowledge to speak and it is the
privilege of the wisdom to listen - Hodly’s

31. • Guide: 3 (B) - CPR
– Impaired Consciousness - From Stroke Resuscitation is
rarely successful Schneider 1993
• Guide: 4(B) Investigations:(Sagar 1995)- 435
PTS)
– Chest x-ray 16% ABN
– Only 4% change clinical management
– Order x-ray chest if WT Loss or chest symptoms
present
Opinion is ultimately determined by the feelings
and not by the intellect

32. • Guide 5: (B) ECG:
– Cardiac cause of Death (30 days) Ebrahim 1990.
– All conscious patients to have ECG
• Guide 6: (C) CT:
– Routine CT Head is a Intell lazy approach
– King’s fund forum(1988) gives useful framework
– Weir 1994 Clinical scoring cannot distinguish
Do CT if a) Uncertainty of Stroke
b) If Anticoagulation or Anti Platelet
treatment contemplated
A great many people think they are thinking when
they are merely re arranging their prejudices
W. James

33. • Guide 7:(B) M.R.I.
– Moha 1995, - Unclear for Implications for
clinical practice
– No Routine MRI indication in Acute Stroke
T T
he ruth is fear and immorality are two of the greatest
inhibitors of Performance to progress

34. CT versus MRI :
1. Only a minority of infarction demonstrated within 24
hours. MRI document infarct as early as 6 hours.
2. Anatomic extent and vascular distribution are better
delineated in MRI. Small infarctions are easily seen.
3. Posterior fossa infarctions are better visualised in MRI.
4. MRI tends to demonstrate Prominent white matter
abnormalities than CT which shows grey matter
abnormalities.
5. CT can distinguish between haemorrhage and
infarction 95% cases. MRI demonstrates acute
cerebral infarction earlier than CT.

35. • Guide 8: (B) ECHO no Routine
– Echo in Acute Stroke
– TOE Vs. TTE
– Amer Heart Asson (1997) - same conclusion
– Yield is very low. (Leung 1993; Chambors
1997)
– Only when ABN ECGS - change clinical
management
A true com itm is a heart felt prom to y
m ent ise ourself
fromwhich y will not back down -
ou
D. Mcnally

36. • Guide 9: (A) - Dopp scan for selected PTS:
– 80% > more benefits from Endarterectomy
– Minor stroke -No disability
– Subst Storke -Good recovery do doppler
– Medically fit
Serious, sincere, systematic studies,
surely secure supreme success

37. • Guide 10: (B) Management:
– Fever (Worst Prog.) Reith 1996
– Hypoxia ( Moroney 1996) - Exac. by seizures
Pneumonia and Arrythmias - Worst outcome
– Hyperbaric O2 ineffective (Nighoghossaln
1995)
– Haemodilut. Plasm Expanders; venesection
– No evidence for efficacy (As plund - 1997)
Check ABG only if Hypoxia suspected.
Why is thought, being the secretion of the brain,
more wonderful than gravity, a property of matter?

38. • Guide 11: (A) Steroids and Hyperosmolar
agents Unproven treatment - should not be
used
– Tumor oedma responds but not cytotoxic
stroke oedma qialbash 1997 - No effect on
survival or improv. In funct. Outcome
– Manntol - (Boysen 1997) - short term effective
statistically in conclusive
God is a comedian performing before an audience
that is afraid to laugh

39. • Guide 12: (B) - Blood Pressure
– Defer - acute reduction of BP - 10 days unless
HT Encephalopathy or adrtic dissection present
– Moris 1997 - Increase BP - falls in 10 days
– UK - 5mm in D.B.P. 1/3 storke - Low BP
prompt correct of hypovoll. and withdrawal of
hypotonic drugs
– Collins 1994 - HT - Prim. stroke prevent
– Neal 1996 (Current RCT) - HTs in stroke
survivors -study needed
Man is made by his beliefs; as he beliefs, so he is

40. • Guide 13: (A/B) - AF
– AF / ISCH Stroke/ Mild disability - warfarin
after 48 Hrs (Longer for larger)
– Aspirin for others
• EAFT 1995 Less than 2 PT - No effect
• SPAF 1996 > 5 - Bleeding
The word shall perish not for lack of wonders but lack of wonder

41. • Guide 14:(B/C) - Blood sugar
– Weir (1997) > 8 mm d/Lit - Poor outcome
– Acute MI + 11 mm d/Lit - Intensive Insulin -
improved (Malmberg 1997)
• Guide 15: (A) Cholesterol
– Prosp. Study collob.: 1993 - Epidem study do
not support
– Blaun 1997: Metranauetic - Chollest & statin
30% decrease - stroke in CAHD patients.
– Sacks 1996 - Tot chol: decrease to 4.8
mmol/Lit benefits

42. • Guide 16: (A/C) Deep vein thrombosis
– Kalra 1995 - 10 days - stroke Pts - 50%
– Sandercock 1993 - Pul embol 6-16% only
– Ist 1997 - 5000 IV or 12500 twice daily -
Hemorrage greater
– Gradual stocking value - useful in Surg - pts but
its value not evaluated - (Wells 1994)
– Use with caution - if periph artery insuf. is
present hence do not use heparin on stockings.
In any field, find the strangest thing and explore it

43. Indications for Carotid Endarterectomy
Degree of Carotid Stenosis Recommendation
by NASCET criteria
Symptomatic disease
70% to 99% CEA
50% to 69% CEA if in high risk group (men and patients
with hemispherical TIAs or strokes)
<50% Medical management (risk factor control +
aspirin 50-325mg/day.
Asymptomatic disease
>60% Consider CEA

44. • Guide 17: (A/B) Pressure sure
– Event health care (1995) specialised low
pressure mattress systems to be used than stand
Hospital - mattress
• Manag of infarction
– Guide 18: (A)
• Aspirin 75 - 150 /Day
• 3 yrs 40% reduces of vascular events in 1000 pts
(APTC - 1994)
• Stroke sub type value ? (TACI, PACI, LACI, POCI)
• Dienners - 1996, synergy possibel with clopidogrel
ticlopidine etc.

45. Anti Coagulation
• Warfarin - AF
– In sinus rhythm - uncertain
– Spirit 1997 low dose ABP + Warfarin in TIA &
Minorstorke - Stopped of HE
– Heparin (IST 1997) - Signif. reduction in early
death (12 fewor in 1000) not better than aspirin
– So avoid Heparin (A)
There are sixty trillion cells in the human body

46. • Thrombolysis (A)
• Warlow 1997 - Uncertain clinical benefit at
the expense of greater hazard avoid -
thrombolysis
“Men of Genius Adm ired:
Men of W ealth envied
wom of power feared but only
en
wom of character are trusted”
en
A- Friedman

47. Common Sites and their incidence
Putaminal Haemorrhage - 35%.
Lobar Haemorrhage - 25%
Thalamic Haemorrhage - 10-15%
Caudate Haemorrhage - 5%
Pontine Haemorrhage- 5%
Cerebellar Haemorrhage - 5-10%
Baby hears 30,000 cycles / sec, teenage boy hears 20,000 and
old hears 4,000 cycles / sec

48. • Guide 20: (I) Hemorrhage
– Hankey and hon 1997: Supra tentorial
evacuation for ICH is controversial - Avoid
– Infra tentorial - Yes
– Main Indication - Deteriorating or depressed
consciousness
“Motivation is the Spark that lights
the Fire of Knowledge and
fuels the engine of Accomplishment”

49. Causes of deterioration in stroke
Neurological Non-Neurological
Progression/completion of stroke Infections
Extension/Early recurrence Metabolic derangement
Haemorrhagic transformation of an Drugs
infarct
Developing cerebral edema Hypoxia
Obstructive hydrocephalus Hypercapnia
Epileptic seizures
Incorrect diagnosis

50. 2 2 4 P ts
Guide 21 : Ventilation
131
I n t u b a tio n
93
N o t In tu b
-Decreased level of
consciousness - increased
6 4 D is c h a r 6 7 D ie d
mortality and poor final
3 4 R e d ta g 2 1 d is c h t o
n ver h om e
8 D is c fo r
p a llim a
1 D is c
H om e
outcome
- Absent pupillary light
3 D ie d 7 D ie d 3 D ie d
responses - poor prognosis
It is a great misfortune not to possess sufficient wit to speak well
nor sufficient judgment to keep silent
La Broyers character

51. Two diverging/converging pataways
associated with VaD
Risk factor CVD Ischemic Brain injury
MRI lesion Clinical syndrome
HTN
Arteriosclerosis 1. occlusion complete infarct
lacune  lacunnar state
Arteriosclerosis 2. Hypoperfusion incomplete
infarct WHSM  Bingswanger syndrome
“ He who cannot forgive others destroy the bridge
s
over which he him m pass” - Annoy
self ust

52. Pathogenesis of dementia due to VaD
1. Lacunar hypothesis
2. Binswanger’s subtype of VaD
3. VaD with coexisting Alzheimer’s disease
In all of us, even in good men, there is a
wild - beast nature which peers out in sleep

53. Clinical syndromes
1. Lacunar state --- 85%
2. Strategic infarct dementia(e.g. thalamic
dementia) --- unknown %
3. Binswanger’s syndrome --- 10 – 15%
“The True Art of Memory is
The Art of Attention” - S.Johnson

54. Features suggestive of
vascular dementia
From the history
Onset associated with a stroke
Improvement following acute event
Abrupt onset
From the exam
Findings typical of stroke e.g., hemiparesis,
hemianopia
From imaging
Infarct(s) above the tentorium

55. Patterns of blood supply to the
cerebral hemispheres
Vascular Arterial supply Collateral supply
distribution
Cortex shorter
Corpus callosum Shorter
Sub cortical U fibers Intermediate Inter digitating
External / extreme Intermediate
capsules
Basal Ganglia Long
Centrum semiovale /
PVWM Long

56. Categories of vascular Dementia
Category Clinical presentation
Lacunar infarctions Progressive dementia, focal deficits, or apathetic,
frontal-lobe-like syndrome, may have no stroke history
Single strategic infarctions Sudden onset aphasia, agnosia, anterograde amnesia,
frontal lobe syndrome
Multiple infarctions Step-wise appearance of cognitive & motor deficits
Mixed AD – VaD Progressive dementia with remote or concurrent history
of stroke
White matter infarctions Dementia, apathy, agitation, bilateral cortico-
(Binswanger’s disease) spinal/bulbar signs

57. Diagnosis
Vascular Mechanism of Pathological
distribution Brain injury phenotype
“Infarct”
Single artery Acute ischemia Multiple lacunar
Small arteriole infarcts
Single artery Acute ischemia Single strategically
placed lacunar
infarct
Border zone Chronic White matter
Small arteriole hypo perfusion demyelination and
axonal loss

58. Diagnostic criteria
1. Hachinski’s ischemic score
2. DSM IV criteria
3. ADDTC criteria
4. NINDS – AIREN criteria
5. Binswanger’s criteria
Starving Emotion - Humor Less; Rigid; Stereotype
Repressing Emotion - Literal; Holier than thou
Encouraging Emotion - Performs in Life
Discourage Emotion - Poison Life
Juseph Colins. 1868

59. Short comings
1. Not interchangeable hence four fold rise in
frequency
2. DSM IV R most liberal
3. NINDS- AIREN criteria conservative
4. Gold standard for VaD (pathological definition
difficult)
5. Most of the criteria failed to distinguish between
small and large vessel subtypes
Take time to think; it is the source of power
Take time to read; it is the foundation of wisdom
Take time to work; it is the price of success

60. Diagnosis of Dementia after stroke
4 sets of criteria are used Sens Spec
1.Hachinski ischemic score 89% 89%
< 4 AD / 18, > 7 MID / 18
2. DSM IV 43% 95%
3. NINDS – AIREN 50% 98%
4. ADDTC criteria 50% 90%
A (Neurologist’s) life is like a piece of paper on which everyone
who passes by leaves an impression
- Chinese proverb

61. Clinical characteristics of Neuro
behavioral syndrome of VaD
• Mental changes of dementia with single
brain lesion
• Sub cortical infarcts
• Multi Infarct Dementia: -
• Sub cortical arteriosclerotic
leukoencephalopathy
“ We Sometimes think we have forgotten something when
in fact we never really learned it in the first place”
Imp.Your Memory Skills

62. AD Vs VaD
AD VaD
Neuro transmitter defect Hemodynamic defect
Female predominance Male predominance
Gradual onset Abrupt onset
Steady deterioration Stepwise deterioration,
fluctuating course
BP normal Hypertension
No history of stroke History of stroke
Global decline in cognitive function Focal neurological symptoms and
signs
Unlikely to respond to treatment May respond to a drug which modifies
microcirculation and enhance cerebral
tissue perfusion

63. Prognosis
1. Risk factors
• Advanced age
• Education
Develops dementia
• Lacunar subtype following ischemic
• Lt. Hemisphere CVA stroke
• Non white
Whatever the Mind can conceive and Believe,
the mind can Achieve
Napoleon Hill

64. Prognosis contd….
2. In Lacunar stroke - Leukoariosis is
a poor prognosis
3. Recurrence of stroke
Hence
• Atrophy
• cognitive impairment
• WMSH are inter related in VaD
Many Ideas grow better when transplanted into another
mind than in the one where they sprang UP
O.W. Holmos

65. Prognosis contd..,
Neuro imaging phenotype
• CT lucency (lacunes and leukoariosis)
• MRI hyper intensity (lacunes and WMSH)
At twenty the will rules
At thirty the intellect
At forty the Judgment

66. Prevention and Treatment of
vascular dementia
I. Brain at risk stage
The aged
Hypertensive
Smokers
Diabetics
Atrial fibrillators
Cardiac patients
When they tell you to grow up,
they mean stop growing
P. Diccaso

67. II. Pre-dementia stage
Patients with TIA
Patients with stroke
Patients with subtle cognitive
infarctions
Patients with silent cerebral infarctions
Expert is one who think to his
chosen mode of ignorance

68. III. Dementia stage
Cardiac embolism
Atherosclerotic cerebrovascular disease
Hypertensive cerebrovascular disease
Maintaining the right attitude is easier than
regaining the right mental attitude

69. Potential therapies of
vascular dementia
1. Brain at risk stage
Smoking cessation
Exercise (prevention and management of diabetes)
Diet (control of diabetes, hyperlipidemias, obesity)
Antihypertensives (ACE inhibitors and ca++ channel-
blockers maybe particularly suitable)
Lipid lowering agents
Anticoagulants (for atrial fibrillation)
Aspirin (for selected patients at high risk)

70. 2. Pre-dementia stage
Carotid endarterectomy (symptomatic patients with
-carotid stenosis of 70-99%)
Anticoagulants
Aspirin
Ticlopidine
Agents that interfere with amyloid deposition vessels
Ca++ channel blockers (pre treatment to attenuate
-effect of infarcts)
NATURE, TIME AND PATIENCE
are the 3 great physicians

71. 3. Dementia stage
Antidepressents
Antihypertensives – 6 mm of Hg reduction in systolic or diastolic
BP -reduces the risk of stroke by 40%
Cholinergics - Tacrine, Galantamine, rivastigmine, donepezil
NMDA antagonist – Memantine
Aspirin
Ticlopidine
A woman’s desire for revenge outlasts all her other emotions

72. Prevention & Treatment
Anti dementia drug trials (not based on subtype of VaD)
Alkaloid derivatives
(hydergine or nicergoline)
Pentoxyfylline
Piracetam Modest benefit
Memantine
Donepezil
Gingko biloba
Give us the GR ACE to acce pt with se re nity the thing s that canno t be
chang e d the COURAGE to chang e the thing s that sho uld be chang e d
and the WISDOM to kno w the diffe re nce

73. Strategies to prevent –
STROKE-TO-DEMENTIA
TEN-STEP APPROACH
1. Treat hypertension optimally
2. Treat diabetes
3. Control hyperlipidaemia, use dietary control for
diabetes, obesity and hyperlipidaemia
4. Persuade patients to cease smoking and decrease
alcohol intake
5. Prescribe anticoagulants for atrial fibrillation
6. Provide antiplatelet therapy for high risk patients
Thought is the labour of the intellect
Reverie is its pleasure

74. Strategies to prevent –
STROKE-TO-DEMENTIA contd…
7. Perform carotid endarterectomy for severe (>70%)
carotid stenosis
8. Recommend lifestyle changes (e.g., weight loss, exercise,
reduce
stress, decrease salt intake)
9. N-methyl-D-aspartate receptor antagonists, antioxidants)
10. Intervene early for stroke and transient ischemic attacks
with neuroprotective agents (e.g., propentofylline,
calcium channel antagosists, - ? Rivastigmine

75. READ not to contradict or confute
Nor to Believe and Take for Granted
but TO WEIGH AND CONSIDER
THANK YOU
“My Opinions are founded on knowledge
but modified by experience”