intracerebral hemorrhage in young adults

1. DR ASHISH SHARMA
SR 1 NEUROLOGY
GMC KOTA
1
INTRACEREBRAL
HEMORRHAGE IN YOUNG
ADULTS

2. Defining ‘Young’
2
 A young adult patient with ICH is usually defined as aged
between 18 years and 50 years.
 ICH in young adults differs from that in older individuals in
respects to spectrum of risk factors, triggers and
underlying cause.
 Indians in general may probably be more susceptible to
stroke but there is no age-specific higher susceptibility for
the young .

3. INCIDENCE OF ICH IN YOUNG
3
 Of all strokes, ICH accounts for 10-30 %.
 In contrast to past advances with ischemic stroke
prevention, ICH incidence has remained steady.
 The incidence ICH has an annual incidence of ~5 per
100,000 individuals in young adults .
 The incidence of ICH in Asian individuals is roughly double
that in either black or white people.
van Asch, C. J. et al. Incidence, case fatality, and functional
outcome of intracerebral haemorrhage over time, according to age,
sex, and ethnic origin: a systematic review and meta-analysis.
Lancet Neurol. 9, 167–176 (2010).

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 The ratio of ICH to ischaemic stroke was 1:1.5–2.0 in young adults
is more to 1:5.4 in individuals >75 years of age.
 In a meta-analysis in 2010, the incidence of ICH in people aged
<45 years was 1.9 per 100,000 individuals which is tenfold for age
45–54 years 20-fold for aged 55–64 years .
 2019 Global Burden of Diseases, Injuries, and Risk Factors study
revealed significant increase in the incidence of ICH in people
aged 20–64 years in low-income and middle-income countries.
Marini, C., Russo, T. & Felzani, G. Incidence of stroke in
young adults: a review. Stroke Res. Treat. 2011, 535672
(2010

5. RISK FACTORS OF ICH
5
 Male gender
 Hypertension
 diabetes.
 Menopause .
 current cigarette smoking .
 a high alcohol intake (≥2 drinks daily)
 a high caffeinated drink intake (≥5 drinks daily)
 Anticoagulant/antiplatlet use
Feldmann, E. et al. Major risk factors for intracerebral
hemorrhage in the young are modifiable. Stroke 36, 1881–1885
(2005).

6. Female-specific risk factors
6
 Pregnancy and the post- partum period are virtually
exclusive to young individuals
 Advanced maternal age
 black ethnicity
 pre-existing hypertension
 gestational hypertension
 pre-eclampsia, eclampsia , coagulopathy and
tobacco use all independently increase the risk of
pregnancy related ICH.
 cerebrovascular disease, eclampsia and HELLP seem
to be the leading causes of pregnancy related ICH.

7. Proportion (%) of first-ever stroke by type
and age groups (hemorrhagic stroke)
7

8. Genetic risk factors
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 Genetic factors play a greater part in ICH in young
adults .
 patients with autosomal dominant familial cerebral
cavernous angioma found that variants in three genes
(KRIT1, CCM2 and PDCD10) account for 85–95% of
all familial cases of this disease.
 The proteins produced form junctions that connect
neighbouring blood vessel cells and interact with each
other to strengthens the interactions between cells
and limits leakage from blood vessels.

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 50% of patients with AD capillary malformation–AVM syndrome
have RASA1 mutations .
 Hereditary haemorrhagic telangiectasia (AD) most patients have
causative mutations in either ENG (encoding endoglin) or
ACVRL1 (encoding serine/threonine-protein kinase receptor R3 .
 In 2017, eight genes (APP, ADA2, COL4A1, COL4A2, GLA, HTRA1,
NOTCH3 and TREX1) were reported to be associated with
Mendelian inheritance of small-vessel disease .
 A single locus in COL4A2 was associated both with deep ICH and
lacunar ischaemic stroke, pointing towards a shared pathology .

10. CAUSES OF ICH IN YOUNG
ADULTS
S
T
R
U
C
T
U
R
A
L
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 Arteriovenous malformation(mc)
 aneurysm
 Cavernoma
 venous angioma
 dural arteriovenous fistula
 capillary telangiectasia
 moyamoya vasculopathy
 primary and secondary (metastatic)
tumours
 von Hippel–Lindau disease
 developmental venous anomalies,
dolichoectasia and intracranial

11. M
E
D
I
C
A
T
I
O
N
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 Anticoagulants
 Antiplatelet drugs
 Thrombolytics
 Selective serotonin reuptake inhibitors
 Drug abuse :
 amphetamine
 methamphetamine
 cocaine(mc)
 crack
 heroin
 phencyclidine, methadone, ephedrine,
pseudoephedrine,pentazocine.

12. A
M
Y
L
O
I
D
A
N
G
I
O
P
A
T
H
Y
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 Icelandic and Dutch forms of hereditary
cerebral haemorrhage with amyloidosis
 cerebral amyloid angiopathy is extremely
rare in patients with ICH <55 years of age

13. S
Y
S
T
E
M
I
C
D
I
S
E
A
S
E
S
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 Severe liver disease
 Renal insufficiency
 Glomerulonephritis
 HIV / AIDS
 E ndocarditis or septic embolism
 pregnancy and the postpartum period
 eclampsia
 vasculitides,
 HELLP
 Reversible cerebral vasoconstriction syndrome
 posterior reversible encephalopathy syndromes
 cerebral venous thrombosis
 connective tissue disorders
 hereditary haemorrhagic telangiectasia (Osler–
Weber–Rendu disease)
 lightning or heat stroke
 haematological diseases and coagulopathies

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 HYPERTENSION :
Primary and secondary causes of hypertension .
 UNDETERMINED:
No clear cause of ICH could be detected after
adequate investigations or the patient could not be
properly investigated
• Persons younger than 35 years of age most
commonly present with a structural cause of ICH,
whereas older individuals most commonly have
hypertension as the cause of ICH
Meretoja, A. et al. SMASH-U: a proposal for etiologic
classification of intracerebral hemorrhage. Stroke 43, 2592–
2597 (2012).

15. PRIMARY INTRACEREBRAL HEMORRHAGE
15
 Primary ICH, accounting for 78 to 88 % of all
cases in young.
 Rupture of small penetrating arteries damaged by
chronic hypertension regarded responsible for
approximately 70% of primary ICH.
 half of hypertension-related ICH locates deep in
the basal ganglia, thalamus, periventricular gray
matter, or brain stem, 30% in superficial areas, and
rest in cerebellum .
 These areas are perfused by the thin perforating
arteries that rise directly from the large basal
cerebral arteries, and are directly exposed to the
harmful effects of hypertension.

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 pathological changes induced by hypertension
such as degeneration in the vessel wall smooth
muscle, which is replaced by collagen and intimal
hyalinization, and development of small miliary
aneurysms associated with thrombosis leading to
microhemorrhages.
 The atherosclerotic changes, or “lipohyalinosis”,
result in development of noncompliant narrowed
vessels that are susceptible to both sudden
occlusion (lacunar infarction) and rupture (ICH).
 CAA is possible cause of ICH in patients older
than 55 years with single cortical or subcortical
hemorrhage without another cause, multiple
hemorrhages with a possible but not a definite
cause, or some hemorrhage in an atypical
location.

17. SECONDARY INTRACEREBRAL HEMORRHAGE
17
 vascular structural anomalies are important
causes of secondary ICH.
 Arteriovenous malformation (AVM), cavernous
hemangioma, intracranial aneurysms, and
Moyamoya disease, they constitute
approximately 5% of all ICH.
 AVMs are vascular lesions, in which blood flows
from arteries to veins without capillaries . They
are most likely congenital but not hereditary, and
their most common clinical presentation is ICH.
 Cavernous hemangiomas, another type of
vascular malformation, have less blood flow, and
usually cause epilepsy.

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 Oral anticoagulation associates nearly 20% of all
ICH increased in no due to increased use
nowadays.
 OAC use is associated with larger initial
hematomas, hematoma expansion and
neurological deterioration in the first 24 to 48
hours.
 Eclampsia acutely raises blood pressure, and by
the same mechanism or by reversible cerebral
vasoconstriction syndrome , pheochromocytoma,
glomerulonephritis, and strenuous physical
activity, may also cause ICH.

19. REVERSIBLE CEREBRAL VASOCONSTRICTION
SYNDROME
19
 Reversible cerebral vasoconstriction syndrome (RCVS) deserves attention, as
it is an important and under-recognized cause of ICH in young patients.
 RCVS most commonly occurs in individuals aged 20–50 years and shows a
strong female bias.
 RCVS is characterized by recurrent thunderclap headache attacks of varying
durations associated with transient, non atherosclerotic and non
inflammatory bilateral segmental constriction of the cerebral arteries
 Other clinical manifestations of RCVS are seizures and focal neurologi cal
deficits.
 Convexity subarachnoid haemorrhage and ICH manifest mainly during the
first week.
 whereas ischaemic events usually occur during subsequent weeks.

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 Catheter angiography remains the gold standard for depicting RCVS,
which manifests as a bilateral ‘string-of-beads’ pattern.
 CT angiography (CTA) and magnetic reso nance angiography (MRA)
have reduced sensitivity for detecting RCVS.
 In approximately one-third of patients with RCVS, angiography
conducted during the first week might not reveal the characteristic
pathology.
 The characteristic angiographic findings typically disappear within
12 weeks of RCVS .
 Cerebrospinal fluid (CSF) samples from patients with RCVS will show
normal or near-normal leukocyte and protein levels, which can help to
distinguish RCVS from vasculitis.
 In general, the more extensive the diagnos- tic workup of young
patients with ICH, the higher the likelihood of identifying a definite
structural or systemic underlying cause.

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FEATURE POSSIBLE ICH
MECHANISM
DIAGNOSTIC TOOL
Drug abuse • Induced hypertensive
ICH • Drug associated
toxic vasculopathy
or vasculitis
• Reversible cerebral
vasoconstriction
syndrome
Urine toxicology
screen
Injectable drug abuse Infectious endocarditis • Urine toxicology
screen
• Blood cultures
Sickle cell disease Moyamoya
vasculopathy
Haemoglobin
electrophoresis
Headache for days to
weeks preceding the
acute presentation
• Cerebral vein
thrombosis
• Haemorrhagic brain
tumour or metastasis
• Reversible cerebral
Advanced imaging

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History of venous
thromboembolism or
hypercoagulability
Cerebral vein
thrombosis
Advanced imaging
Current or former
malignancy
Haemorrhagic brain
tumour or metastasis
Advanced imaging
Migraine with aura or
stereotyped aura
localizing to the
anatomical region
where ICH occurred
Arteriovenous
malformation
Advanced imaging
History of haemorrhage
in same location
Cavernoma Advanced imaging

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Fever at presentation or
recent or concurrent
bacterial infection
Infective endocarditis Sedimentation rate
Blood culture
Family history of ICH • Familial cavernoma
syndrome
• Hereditary
haemorrhagic
telangiectasias
• COL4A1 mutations
Genetic testing and
councelling
Pulsatile tinnitus or bruit • Arteriovenous fistula
• Cerebral venous
thrombosis
Advanced imaging
Haemophilia or another
inherited coagulopathy
ICH associated with
coagulopathy
• PT and/or APTT
• Specialized
coagulation
testing

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25. CLINICAL PICTURE OF INTRACEREBRAL HEMORRHAGE
25
 The clinical presentation of ICH depends on its
size and location as well as presence of IVH.
 The classic presentation of ICH is sudden onset of
a focal neurological deficit that in contrast to other
stroke subtypes progresses gradually over
minutes to hours
 It usually accompanying headache, nausea,
vomiting, decreased consciousness, and elevated
blood pressure.
 Gradual progression most likely relates to ongoing
bleeding. Only 15% present symptoms at
awakening.
 The most common symptom is headache of
variable intensity and the most common focal

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 Headache is present in about 40% and vomiting
has been reported in 49% for ICH patients
espicially in posterior fossa.
 Clinical signs of increased ICP, such as early
impaired consciousness, nausea, and vomiting
are suggestive of ICH
 Seizures appear in approximately 10% of all
patients with ICH Nearly all seizures occur at the
onset of bleeding or within the first days of ictus.
 More than 90% patients present with elevated
blood pressure (>160/100 mmHg), and symptoms
caused by dysautonomia, such as
hyperventilation, tachycardia, bradycardia, central
fever, and hyperglycemia are also frequent.

27. IMAGING
27
 CT is preferable to MRI in the emergency setting,
although MRI is preferred when time constraints
are less important .
 In diagnosed ICH , further neuroimaging studies
are generally performed to determine underlying
cause .
 The choice of imaging should be based on the
anatomical location of the ICH and suspicion of a
particular cause .
 For example, very young patients, those with
lobar haemorrhage without a history of
hypertension or coagulopathy are likely to have
an underlying vascular cause.

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 Lobar location of ICH was significantly more prevalent in
the younger age, while deep location as more prevalent in
the older age
 CT showed not only low sensitivity (26.5%) in the detection
of structural/local causes but also high specificity (86.3%)
compared with MRI.
 MRI was found to be more sensitive (90.0%) in detecting
structural/local causes compared with any angiographic
imaging (55.5%) including CTA, MRA, or DSA.
 MRI was found to be less specific (87.3%) for
structural/local causes compared with angiography
(97.4%).
 There is a marked decrease in angiographic imaging
sensitivity when performed >2 weeks after ICH onset
compared with early (<2 weeks) imaging

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 CT angiography should be performed acutely preferably
within 2 days of the non-contrast brain CT, except those in
low risk of an underlying macrovascular cause
 DSA is so far the gold standard for detection of AVMs .
 MRI is more sensitive in detection of cavernomas and
tumors.
 If CTA is negative then MR/MR angiography if negative
then DSA (in high suspicion)
 appreciable yield of repeat DSA performed a few weeks
later, especially in lobar ICH, so persistence is often
required

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van Asch CJ, Velthuis BK, Rinkel GJ, et al. Diagnostic yield and
accuracy of CT angiography,MRangiography, and digital subtraction
angiography for detection of macrovascular causes of intracerebral
haemorrhage: prospective, multicentre cohort study. BMJ
2015;351:h5762

32. HEMATOMA EXPANSION
32
 Patients presenting early symptom onset and
receiving anticoagulated are at higher risk for
hematoma expansion.
 The “spot sign” is detected through CTA and is
characterized by a spot of contrast enhancement
inside the hematoma.
 The “leakage sign” is more sensitive than the spot
sign and the image is acquired 5 minutes after CTA
(late phase).
 Images from both arterial and late phases are

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 The “island sign”, “blend sign”, “black hole sign”, and “satellite
sign” are seen in the non-contrasted head-CT.
 The “island sign” is defined as scattered small hematomas apart
from the main hematoma .
 The “blend sign” is defined as blending of a relatively
hypoattenuating area with adjacent hyperattenuating region
within a hematoma.
 The “black hole sign” is defined as a relatively hypoattenuating
area (black hole) encapsulated within the hyperattenuating
hematoma.
 the “satellite sign” is defined as small (maximal diameter <10
mm) hemorrhage close to but completely isolated from the main
hemorrhage in at least a single slice.
Deng L, Zhang G, Wei X, Yang WS, Li R, Shen YQ, et al. comparison
of satellite sign and island sign in predicting hematoma growth and
poor outcome in patients with primary intra cerebral hemorrhage.
World Neurosurg. 2019 Jul;127:e818-e825.

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(A) Cerebellar intracerebral hemorrhage with “blend sign” (white arrows)
and “black-hole sign” (yellow arrow).
(B) Lobar intracerebral hemorrhage with “satellite sign” (yellow arrow).
(C) Deep intracerebral hemorrhage with “island sign” (yellow arrows).

35. EARLY MORTALITY AFTER INTRACEREBRAL HEMORRHAGE
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 ICH is the most catastrophic subtype of strokes with high
mortality and morbidity.
 case-fatality at 1 month was 40%, increasing to 54% at one-
year.
 early mortality rates between 40% and 50 %, with half of
deaths occurring within the first 2 days.
 30% of the survivors after acute phase were left in a vegetative
state
 20% to 25% of the survivors were fully independent at 6
months
Go, G. O. et al. The outcomes of spontaneous
intracerebral hemorrhage in young adults — a clinical
study. J. Cerebrovasc. Endovasc. Neurosurg. 15, 214–220
(2013

36. POOR OUTCOMES IN ICH
36
 Hematoma volume > 30
mL
 Arrival GCS < 13
 Presence and volume of
IVH
 Infratentorial hematoma
location
 Age > 80
 Imminent herniation
 Hydrocephalus
 OAC use
 Antiplatelet use
 Hyperglycemia
 Hypertension
 Ischemic heart disease
 Atrial fibrillation
 Diabetes
 chronic kidney disease
Poon MT, Fonville AF, Al-Shahi Salman R. Long-term
prognosis after intracerebral haemorrhage: Systematic
review and meta-analysis. J Neurol Neurosurg Psychiatry.
2014;85:660-667.

37. PREDICTION SCORES IN ICH
37
 The NIHSS used for ischaemic stroke is also
valuable in ICH, but its utility is limited by frequent
occurrence of depressed consciousness in ICH.
 The GCS score is the most useful initial
evaluation because of its similar prognostic value
to NIHSS, its simplicity and its incorporation in the
ICH score.
 Haematoma volume independently predicts
haematoma expansion and early mortality.

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FUNC SCORE

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63. REFERENCES
63
 BRADLEYS TEXTBOOK OF NEUROLOGY
 Tatlisumak, T., Cucchiara, B., Kuroda, S. et al. Nontraumatic
intracerebral haemorrhage in young adults. Nat Rev Neurol 14,
237–250 (2018).
 Riku-Jaakko Koivunen, Elena Haapaniemi, Jarno Satopää, Mika
Niemelä, Turgut Tatlisumak, Jukka Putaala, "Medical Acute
Complications of Intracerebral Hemorrhage in Young Adults",
Stroke Research and Treatment, vol. 2015, Article ID 357696, 7
pages, 2015.

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 2022 Guideline for the Management of Patients With
Spontaneous Intracerebral Hemorrhage: A Guideline From
the American Heart Association/American Stroke
Association.
 McGurgan IJ, Ziai WC, Werring DJ, et al Acute intracerebral
haemorrhage: diagnosis and management , Practical
Neurology 2021;21:128-136
 Elmegiri M, Koivunen R-J,isumak T, Putaala J and Martola
J(2020) MRI Characterization of Non-traumatic
Intracerebral Hemorrhage in Young Adults. Front. Neurol.
11:558680.doi: 10.3389/fneur.2020.558680

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YOU