the powerpoint highlights on the etiopathogenesis,clinical features & approach to pediatric stroke

1. PEDIATRIC STROKE
CHAIRPERSON - DR SHIVAPRAKASH N.C
MODERATOR - DR MADHAVA KAMATH
PRESENTOR - DR G HARSHAVARDHAN

2. INTRODUCTION
DEFINITION
TYPES
EPIDEMIOLOGY
ETIOLOGY
PATHOPHYSIOLOGY
CLINICAL FEATURES
DIFFERENTIAL DIAGNOSIS
APPROACH TO DIAGNOSIS & EVALUATION
MANAGEMENT & REHABILITATION

3. HISTORY
• The word stroke was used as a synonym for
apoplectic seizure as early as 1599.
• Apoplexy (from Ancient Greek ,meaning 'a striking away') is
bleeding within internal organs and the accompanying
symptoms. For example, ovarian apoplexy is bleeding in the
ovaries. The term formerly referred to, what is now called
a stroke.
• The word apoplexy was sometimes used in medieval era to
refer to the symptom of sudden loss of consciousness
immediately preceding death.

4. • Episodes of stroke and familial stroke have been reported
from the 2nd millennium BC onward in ancient
Mesopotamia and Persia.
• Hippocrates (460 to 370 BC) a greek physician was first to
describe the phenomenon of sudden paralysis that is
often associated with ischemia.

5. • In 1658, Johann Jacob Wepfer ,a swiss pathologist(1678)
identified the cause of hemorrhagic stroke when he suggested
that people who had died of apoplexy had bleeding in their
brains. He also identified the main arteries supplying the brain,
the vertebral and carotid arteries, he suggested
that apoplexy might be caused by a blockage to those vessels.
• Rudolf Virchow , (1869) a german pathologist first described
the mechanism of thromboembolism as a major factor.
Virchows traid

6. HIPPOCRATES RUDOLF VIRCHOW JACOB WEPFER

7. • The term cerebrovascular accident was introduced in
1927, Cerebrovascular insult was used interchangeably in
later days
• The term brain attack was introduced for use to underline
the acute nature of stroke according to the American
Stroke Association, who since 1990 have used the term,
and is used colloquially to refer to both ischemic as well as
hemorrhagic stroke
• Brain attack/cerebrovascular accident/insult (CVA/CVI)

8. INTRODUCTION
• The term Childhood Stroke refers to stroke in children
aged between 1-18 years of age.
• Stroke is an important cause of acquired brain injury in
newborns & children.

9. DEFINITION
• WHO - Clinical syndrome of rapidly developing focal or
global disturbance of brain function lasting more than 24
hours or leading to death with no obvious nonvascular
cause.
• The duration cut-off of 24 hours is in the context of defining
another vascular event i.e., Transient Ischemic Attack (TIA) as
a sudden, focal neurologic deficit that lasts for < 24 hours, of
presumed vascular origin, confined to an area of brain or eye
perfused by a specific artery.

10. Definition encompasses tissue criteria i.e., presence or absence
of tissue infarction to differentiate
- Stroke ( tissue infarction) vs TIA (no tissue infarction)
Acute stroke is neurologic emergency.
Unlike stroke in adults, there are a diverse group of disorders
producing stroke in newborn & children.

11. TYPES-
• Stroke is broadly classified into 2 types, based on primary
pathophysiology of the disease :
 ISCHEMIC STROKE ( interruption of blood flow to a part
of brain)
 HEMORRHAGIC STROKE (rupture of blood vessels with
bleeding into the cerebral parenchyma).

13. DIFFERENCE BETWEEN ADULT STROKE & PEDIATRIC
STROKE
• In adult: chronic risk factors
• In children:
1- congenital and developmental risk factors
2- rare
3-subtle presentation*
4- wide differential diagnosis
*Among neonates, signs of hemiparesis are generally
not seen before the first six months to one year of life

15. INCIDENCE
• Stroke is among the top ten neurological causes of death in
childhood with the highest mortality in the first 12 months of
life.
• The incidence of stroke is around 5 /100,000-population
• Approximately one third of all cases occur in children less than
one year of age.
• Stroke affects between 1 in 2,300-5,000 newborns.

16. • 20-40% of children have recurrent strokes.
• 50-85% of survivors of stroke will be left with long term
problems which may include seizures, physical disability,
speech or learning difficulties

17. THE KEY ISSUES FOR CHILDREN AND THEIR FAMILIES
INCLUDE:
• Lack of awareness amongst the community and primary care
doctors about childhood stroke.
• Lack of understanding about the causes of stroke.
• Delayed recognition of stroke in children. The median time from
onset of pediatric ischaemic stroke to diagnosis is over 22
hours limiting the ability to use treatments to dissolve clots in
the brain.
• Limited evidence about the best form of treatment to prevent
further strokes.

18. • Of all pediatric strokes:-
Ischemic strokes 55%
Hemorrhagic strokes 45%
Stroke in an adult :-
Ischemic strokes 80-85%
Hemorrhagic strokes 15-20%

21. BLOOD SUPPLY OF BRAIN
• Brain: 700-800 ml blood/min (55ml/100g/min)
• < 30 ml/100gm/min: leads to ischemia
• 80 % blood to gray matter & 20 % to white matter.
Blood supply to brain-
• Carotid system- 2 Internal Carotid arteries
• Vertebro-basilar system- 2 Vertebral arteries

22. Internal carotid artery has 4 portions:
• 1.Petrous PC3
• 2.Cervical
• 3.Cavernous
• 4.Cerebral

23. Branches of Cerebral portion of Internal Carotid artery are:
• Middle cerebral artery MAAPO
• Anterior cerebral artery
• Anterior choroidal artery
• Posterior communicating artery
• Ophthalmic artery

24. Vertebro basilar system
• Brain stem, Thalamus, temporal lobe-inferior portion,
occipital lobe
• 1. Vertebral artery
• 2. Basilar artery
• 3. Posterior cerebral artery

25. CIRCLE OF WILLIS
• 1. Middle cerebral artery (MCA)
• 2. Anterior cerebral artery (ACA)
• 3. Posterior cerebral artery (PCA)

27. CLASSIFICATION-

31. ARTERIAL ISCHEMIC STROKE ( AIS )
• Arterial blood reaches the brain via the anterior (internal carotid)
& posterior (vertebrabasilar) circulations, converging at the circle
of Willis.
• Strokes most often involve the middle cerebral artery territory
but can occur in any cerebral artery of any size.
• AIS is the focal brain infarction that results from occlusion of these
arteries and is a leading cause of acquired brain injury in children
with the perinatal period carrying the highest risk.

32. • The diagnosis of stroke in children is frequently delayed. This
is a consequence of subtle and nonspecific clinical
presentations.
• The acute onset of a focal neurologic deficit
in a child is stroke until proven otherwise.
The most common focal presentation is hemiparesis, but acute
visual, speech, sensory, or balance deficits also occur.
Children with these presentations require urgent neuroimaging.

33. Epidemiology
• Incidence depends on age & geographic location
• The reported incidence ranges from 1.2 cases / 1,00,000
population to 13 cases/1,00,000 children.
International pediatric stroke study shows significant male
predominance for childhood ischemic stroke regardless of
age & stroke subtype.
In infants- (1.25 cases/1,00,000 children per yr) major cause
– CHD & Perinatal Asphyxia.

34. • Stroke incidence decreases to nearly half if infants are
removed from the study population.
• There is no population based data regarding true burden
of childhood stroke in India, as per hospital based surveys-
• Childhood stroke constitute 5-15% of all strokes in the
young & 0.7 % of all pediatric admissions.

35. ETIOLOGY
• The predominant causes for ischemic stroke in children
can be grouped into-
 STRUCTURAL HEART DISEASE
 VASCULOPATHIES ( Inflammatory & non inflammatory )
 HEMATOLOGICAL DISORDERS
 PROTHROMBOTIC STATES ( inherited & acquired )
The prevalence of risk factors varies depending on the
geographical location.

36. ETIOLOGY OF ISCHEMIC STROKE IN CHILDREN
Structural heart disease & thromboembolism:-
• Cardiac causes are more prevalent in younger children (up to
2yrs).
• Thromboembolism being the main pathophysiological
mechanism.
• Embolic stroke is an important complication of cardiac
surgery during intraoperative & immediate postoperative
period (ex- Fontan operation)

37. • Congenital heart disease
• Rheumatic heart disease
• Infective endocarditis
• Cardiomyopathies, Arrhythmias
• Prosthetic ,prolapsed valves
• Cardiac interventions ( Fontans operation)
• Neck trauma & craniovertebral junction anomalies

38. Haematological causes-
• Children with sickle cell disease are highly vulnerable to
cerebrovascular events, with incidence of stroke as high as 285
cases /100000 children.
• 25% of pts with sickle cell anemia develop cerebrovascular
complications of which 80% are under 15 yrs of age. Mean age
of stroke is 7 yrs & recurrence risk is 67%

39. • Hemoglobinopathies – Sickle cell anemia
• Thrombocytosis
• Polycythemia
• Lymphoreticular malignancies

40. VASCULOPATHIES-
• INFECTIVE VASCULITIS –Pyogenic /fungal /tuberculosis/ AIDS /
mycoplasma
• NONINFECTIVE VASCULITIS –SLE /polyarteritis nodose /Takayasu
arteritis
• Post varicella angiopathy
• NON-INFLAMMATORY VASCULOPATHIES- Moyamoya disease
/migraine/ Marfans syndrome/ Ehler Danlos syndrome/
fibromuscular dysplasia

41. • Infective vasculitis/non infective inflammatory vasculitis & non
inflammatory vasculopathies are other major causes of ischemic
stroke. Of these moyamoya disease is highly prevalent in japan, south
east Asian countries.
MOYAMOYA DISEASE –
• Is a vasculopathy with progressive stenosis of supraclinoid portion
of internal carotid arteries, with dev of extensive collaterals from
other vascular territories.
• The appearance of these collaterals on angiogram is given the name
“ puff of smoke “

42. MOYAMOYA SYNDROME
• When the similar clinical & radiological findings are seen in assoc.
with conditions like downs syndrome, neurofibromatosis,
autoimmune disease, cerebrovascular atherosclerosis, cranial
irradiation or cerebral neoplasm ,it is called MOYAMOYA
SYNDROME

44. • Another important childhood vasculopathy is Post varicella
angiopathy [PVA]
• Stroke can be seen in children after varicella infection with latency
period ranging from 2-4 wks to 12 months.
• Commonly seen in anterior circulation
• Diagnosis is confirmed by varicella zoster specific antibodies in CSF.

45. PROTHROMBOTIC STATES
• Inherited & acquired causes
• Account for 20-50% of children with AIS & 33-39% of children with
CVST.
• Protein C ,S deficiency, antithrombin 3 deficiency
• Activated protein C resistance, factor 5 leiden mutation,
prothrombin mutation
• Lupus anticoagulant IgG , IgM
• Elevated lipoprotein A

46. METABOLIC CAUSES -
• MELAS – [ Mitochondrial encephalopathy, lactic acidosis & stroke
like episodes ]
• Leigh disease
• Fabry disease
• Ornithine transcarbamylase deficiency, sulphite oxidase deficiency
• Organic acidemias- methyl malonic acidemia, propionic academia,
glutaric acidemia type 2

47. DRUGS
• Cocaine
• Amphetamine
• Triptans
• Ergots
MISCELLANEOUS RISK FACTORS-
• Iron deficiency anemia

48. ARTERIAL ISCHEMIC STROKE. A HEALTHY 3 YR OLD BOY HAD SUDDEN ONSET OF LEFT-SIDED WEAKNESS. EXAMINATION ALSO
DEMONSTRATED LEFT-SIDED HEMISENSORY LOSS AND NEGLECT. A TO C, DIFFUSION-WEIGHTED MRI SHOWS FOCAL INCREASED
SIGNAL IN THE RIGHT TEMPORAL–PARIETAL REGION IN THE TERRITORY OF THE MIDDLE CEREBRAL ARTERY (MCA). D, APPARENT
DIFFUSION COEFFICIENT MAP CONFIRMS RESTRICTED DIFFUSION CONSISTENT WITH INFARCTION (ISCHEMIC STROKE). E, MR
ANGIOGRAM SHOWS DECREASED FLOW IN THE CORRESPONDING BRANCH OF THE MCA. F, FOLLOW-UP MRI AT 3 MO SHOWS
ATROPHY AND GLIOSIS IN THE SAME REGION.

49. CUT SECTION OF BRAIN SHOWING MCA STROKE

50. PERINATAL ARTERIAL ISCHEMIC STROKE. A TERM NEWBORN DEVELOPED FOCAL RIGHT-SIDED SEIZURES
AT 16 HR OF LIFE. A, DIFFUSION-WEIGHTED MRI ON DAY 2 DIAGNOSES NEONATAL ARTERIAL ISCHEMIC
STROKE BY DEMONSTRATING RESTRICTED DIFFUSION IN THE LEFT MIDDLE CEREBRAL ARTERY TERRITORY.
B, REPEAT MRI AT 12 MONTHS SHOWS CYSTIC ENCEPHALOMALACIA AND SCARRING IN THE SAME
TERRITORY, A SIMILAR APPEARANCE TO CHILDREN DIAGNOSED WITH PRESUMED PERINATAL ARTERIAL
ISCHEMIC STROKE LATER IN INFANCY

51. ETIOLOGY OF POSTERIOR CIRCULATION STROKE
• Ischemic stroke in posterior circulation (vertibrobasilar arteries &
their territories) has slightly different set of causes including
vertebral artery dissection following neck trauma , craniovertebral
junction anomalies apart from haematological & prothrombotic
states.

52. PATHOPHYSIOLOGY
• Thromboembolism is the most common mechanism of stroke
with source of thrombus being either the cerebral arteries or
the heart & major vessels ( cardioembolism).
• The pathophysiology of cerebral ischemia consists of primary &
secondary injury.
• PRIMARY INJURY – implies the cellular dysfunction caused
directly by ischemic insult. the chain of events & derangements
set into motion by the primary injury constitute the secondary
injury.

53. • The prominent in the tissue damage caused by cerebral ischemia is
the presence of a CENTRAL CORE – where ischemia is most
severe with rapid development of tissue infarction & neuronal
cell death.
• The area surrounding the central core , which is marginally
perfused is called the ‘penumbra’.
• Penumbra has the capacity to recover when perfusion is recovered
prompty.
• The balance between cerebral metabolic rate & the supply of
oxygen & glucose determines extent of penumbra, & thus the
severity of stroke.

55. CLINICAL FEATURES
Evolution of symptoms-
Hyperacute to acute in children
The presenting symptoms depend on the anatomical & functional areas of
brain affected.
Common symptoms include-
• 1 or more focal neurologic deficit i.e- Hemiparesis ( most common
presentation)
• Dysarthria
• Aphasia
• Facial nerve palsy
• Hemianopsia/Diplopia

56. • Infants & young children also manifest nonspecific
features like headache ,drowsiness , irritability &
behavioural abnormalities
• Isolated extrapyramidal symptoms like hemidystonia can
be presenting symptom in infants with subcortical strokes
involving perforating arteries.

57. DIFFERENTIAL DIAGNOSIS
• Todds palsy
• Acute disseminated encephalomyelitis [ ADEM ]
• Stroke like episodes in MELAS( mitochondrial encephalopathy
,lactic acidosis & stroke like events)
• Intracranial space occupying lesions [ ICSOL ]
• Posterior reversible encephalopathy syndrome [ PRES ]
• Recurrent episodic hemiparesis.

58. • Todds palsy –transient weakness of one or more body
parts following seizure in those parts, which lasts variably
from 30min- 36hrs.hemiparesis is the most common
manifestation , resolves completely without any
treatment.
• ADEM- most common demyelinating event in childhood.
hemiparesis often a/w encephalopathy. MRI confirms the
nonvascular demyelinating nature of the disorder

59. • ICSOL- inflammatory granulomas-neurocysticercosis,
tuberculoma, pyogenic brain abscess.
• PRES- acute onset encephalopathy with neurological
deficits with acute onset hypertension( predominantly
affects post. circulation)

60. APPROACH TO DIAGNOSIS & EVALUATION
• Neuroimaging – is the cornerstone for arriving at diagnosis of
stroke by confirming the vascular nature & ruling out other
mimicking conditions
• MRI – gold standard for diagnosis of stroke, complemented by
MRA (angiography) /MRV (venography)
• Digital subtraction angiography (DSA) – gold standard for
diagnosis of vasculopathies
• Transcranial doppler (TCD) – non invasive test to measure blood
flow velocity in major cerebral vessels.

62. MANAGEMENT
Stabilization & supportive care-
• Care of airway, breathing, circulation .
• Spo2 to be maintained more than 90% with use of
supplemental oxygen if necessary.
• Aggressive treatment of fever, systemic hypertension,
hypoglycaemia, hypovolemia should be done, as they help in
maintaining adequate cerebral perfusion.
• In children with SCD & Stroke, adequate hydration & exchange
transfusion to keep HbS more than 30% is the mainstay of
treatment.

63. • Seizures & raised ICP should be managed as well
• Raised ICP may be treated using either mannitol/hypertonic
3% saline in the acute phase & hyperventilation for shorter
periods
• Rarely emergent decompressive craniectomy may be needed
in cases with malignant cerebral edema not responding to
med measures /impending risk of herniation.

64. THROMBOTIC THERAPY
So far no conclusive evidence to suggest the safety, efficacy
of thrombolytic therapy
• Anticoagulant therapy-
- acute phase anticoagulation
- long term anticoagulation

65. ACUTE PHASE ANTICOAGULATION
• Use of LMWH-for anticoagulation in acute phase as they
might benefit substantially.
• Ex- carotid, vertebral artery dissection ,suspected inherited
prothrombotic states.
• LMWH –has several advantages: fewer side effects & drug
interactions, less need for monitoring, easy route of
administration (SC)

66. LONG TERM ANTICOAGULATION
• 3-12 Months or more
• Recommended for children with risk of recurrent stroke.
• Used in ischemic stroke, major structural heart disease
with risk of cardioembolism, carotid artery dissection,
inherited prothrombotic states.

67. ANTIPLATELET DRUGS
• Aspirin & clopidogrel
• In children who are advised long term aspirin therapy,
varicella vaccination & annual influenza vaccine is
recommended to reduce the risk of reye syndrome

68. SURGICAL MANAGEMENT
• Revascularization surgeries
• Emergency decompressive craniectomy.
Rehabilitation –
• Physiotherapy-gait training, strengthening of weak muscles
,oromotor stimulation
• Occupational/speech therapy.
• Treatment of comorbid conditions

69. • The MERCI Retriever is a medical device designed to
treat Ischemic Strokes. The name is
an acronym for Mechanical Embolus Removal
in Cerebral Ischemia. Designed by University of California, Los
Angeles in 2001, MERCI was the first device approved in the U.S. to
remove blood clots in patients suffering from acute brain ischemia

70. PROGNOSIS
Factors predicting poor outcome include-
• Cerebral cortex involvement
• Large size of infarct
• Moyamoya disease

73. CEREBRAL VENOUS SINUS THROMBOSIS [CVST]
• Cerebral venous drainage occurs via the cerebral sino
venous system. This includes superficial (cortical veins,
superior sagittal sinus) & deep (internal cerebral veins,
straight sinus) systems that converge at the torcula (
confluence of sinuses) to exit via the paired transverse
and sigmoid sinuses and jugular veins.

75. • In CVST, thrombotic occlusion of these venous structures
can create increased intracranial pressure, cerebral edema, &
in 50% of cases, venous infarction/ hemorrhage (stroke). CVST
may be more common in children than in adults, and risk is
greatest risk in the neonatal period.
• Clinical presentations are typically gradual, variable, and
nonspecific compared to AIS.

76. • Children may present with symptoms mimicking idiopathic
intracranial hypertension, including progressive headache,
papilledema, diplopia secondary to 6th nerve palsy, or with
acute focal deficits, Seizures, lethargy, and confusion are
common.
• Diagnosis requires a high clinical suspicion and purposeful
imaging of the cerebral venous system. Nonenhanced CT is very
insensitive for CSVT, and contrast CT venography or MR
venography is necessary to demonstrate filling defects in the
cerebral venous system.

77. • Since venous occlusion results in increased venous pressure,
there is a tendency for blood vessels to rupture producing
secondary haemorrhage.
• MRI with MRV is the preferred imaging modality in suspected
CVST
• Anticoagulation with LMWH /warfarin –depending on extent
of recanalization of venous sinuses in follow up.
• Ophthalmological screening

79. • Cerebral sinovenous thrombosis. A 9 yr old girl presented with fever and progressive right-sided headache. She
complained of double vision and had papilledema on examination. Axial (A) and coronal (B) CT venography
demonstrates a large thrombus in the right transverse sinus that fails to opacify with contrast (full arrows). Note
normal filling in superior sagittal and in smaller left transverse sinuses (empty arrows, right) and opacification of
the mastoid air cells (hatched arrow, left). Cause was otitis media/mastoiditis with septic thrombophlebitis of
transverse sinus.

80. HAEMORRHAGIC STROKE
• HS includes nontraumatic intracranial hemorrhage and is
classified by the intracranial compartment containing the
hemorrhage.
• Intraparenchymal bleeds may occur in any location,
whereas intraventricular hemorrhage may be isolated or
an extension of intraparenchymal hemorrhage.
• Bleeding outside the brain may occur in the subarachnoid,
subdural, or epidural spaces.

81. TYPES
• Intracranial hemorrhage (ICH), also known
as intracranial bleed,It includes-
• intracerebral bleeds (intraventricular
haemorrhage and intraparenchymal
haemorrhage)
• subarachnoid bleeds
• epidural bleeds
• subdural bleeds

82. • Clinical presentations vary according to location, cause,
and rate of bleeding. Acute hemorrhages may feature
instantaneous or thunderclap headache ( sec to SAH), loss
of consciousness, and nuchal rigidity in addition to focal
neurologic deficits and seizures.
• HS can be rapidly fatal. In bleeds associated with vascular
malformations, pulsatile tinnitus, cranial bruit,
macrocephaly, and high-output heart failure may be
present.

83. - Diagnosis relies on imaging and CT is highly sensitive to
acute HS. However, lumbar puncture may be required to
exclude subarachnoid hemorrhage. MRI is highly sensitive
to even small amounts of both acute and chronic
hemorrhage and offers improved diagnostic accuracy.
- Abusive head trauma with intracranial bleeding in children
may present as primary subdural or parenchymal
hemorrhage with no apparent history of trauma.

84. • Subtle scalp, suborbital, or ear bruising; retinal
hemorrhages in multiple layers; and failure to thrive
should always be sought, and in infants with subdural
bleeds, x-rays performed to rule out fractures.
• Epidural hematoma is nearly always caused by trauma,
including middle meningeal artery injury typically
associated with skull fracture.
• Subdural hematoma can occur spontaneously in children
with brain atrophy because of stretching of bridging veins.

86. GOAL OF REHABILITATION
• Help children with physical disabilities improve FUNCTION
and PARTICIPATE more fully in family, social, educational
and recreational activities.

87. REHABILITATION TOOLS
• Motor and cognitive exercises
• Medications
• Adaptive equipment
• Recreational involvement

88. LOCALIZATION OF HEMIPLEGIA
1. Hemispheric lesion
• a. Cortex - cortical features like seizures, dysplasia.
motor deficits are minimum.
Cortical type of sensory loss - Parietal lobe function-
( loss of tactile localization, 2 point discrimination,
stereognosis, graphaesthesia, sensory inattention ).
• b. Corona radiata - absence of cortical features
motor deficits- unequal weakness of limbs on
C/L side. Either UL>LL or LL>UL.
Dulling of Primary modalities of sensation- touch,
superficial pain, temperature.

89. c. Internal capsule : C/L hemiplegia, uniform weakness of limbs on
C/L side, reduction of primary modalities of
sensation-touch, superficial pain, temp.
Homonymous hemianopia
2. Brain stem : Crossed hemiplegia
I/L LMN cranial nerve palsy
C/L hemiplegia

90. Brain stem
• a. Midbrain : Weber syndrome : I/L 3rd CN & 4th CN palsy,
C/L hemiplegia.
• b. Pons : Millard Gubler syndrome : I/L 6th CN & 7th CN palsy,
C/L hemiplegia.
• c. Medulla : C/L hemiplegia , I/L CN involved

95. STROKE AWARENESS PROGRAMMES

98. REFERENCES-
• NELSONS 20TH EDTN
• CHILD NEUROLOGY – MENKES & SARNAT
• PEDIATRICS PG TEXTBOOK- PIYUSH GUPTA
• FINCHELS PEDIATRIC NEUROLOGY

99. THANK YOU