Recent Developments in the Acute Treatment of Intracerebral ... [PDF]

May 20, 2014 - Intracranial aneurysm. Venous disease. • Cerebral sinus / venous thrombosis. • Dural arteriovenous fi

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Recent Developments in the Acute Treatment of Intracerebral Hemorrhage Christian Stapf Tenured Professor of Neurology Univ Paris Diderot – Sorbonne Paris Cité APHP - Hôpital Lariboisière, Paris Neurovascular Unit Adj. Assist. Professor of Neurology Stroke Center Columbia University Medical Center

New York City 21st Annual Stroke Reception Tuesday, May 20, 2014

Disclosures Stocks None Project Funding Reference Center for Rare Neurovascular Disorders of the Brain and Eye (French Ministry of Health) Trials (< 5 years) ARUBA ongoing Co-PI (Europe) NIH/NINDS, USA HeadPost ongoing Co-PI (France) NMHRC, Australia INTERACT-2 finalized Co-PI (Europe) NMHRC, Australia Advisory Boards, Panel Member, Speaker Fees (< 3 years) European Commission, ESC, SFCNS, WFITN Travels, Accomodation, Admission Fees (< 1year) AHA/ASA Int. Stroke Conference speaker 2013 AHA/ASA Stroke Reception, NYC speaker 2014 AVM World Conference speaker 2014 Neuroradiologie Aktuell speaker 2013, 2014 ESC speaker 2013, 2014 ESNR speaker 2013 European Stroke Congress speaker 2013, 2014 European Stroke University speaker 2013 French Neurovascular Society speaker 2013 Portuguese Stroke Society speaker 2014 Use of Unlabeled / Unapproved Products None

Hôpital Lariboisière, Paris (France)

Columbia University Medical Center

Intracerebral Hemorrhage Recent Developments

Intracerebral Hemorrhage Recent Developments The new generation is coming…

Intracerebral Hemorrhage Recent Developments



Intracerebral Hemorrhage Recent Developments

No dedicated ICH classification…

No standardized ICH diagnostic workup… No specific ICH treatment… Uncertainty regarding preventive intervention for unruptured, hemorrhageprone lesions…

Intracerebral Hemorrhage Recent Developments

No dedicated ICH classification…

No standardized ICH diagnostic workup… No specific ICH treatment… Uncertainty regarding preventive intervention for unruptured, hemorrhageprone lesions…

Intracerebral Hemorrhage Classification Ischemic stroke • Harvard Stroke Registry / NINDS Stroke Databank • Oxford Community Stroke Project classification (OCSP) • TOAST (Trial of Org 10172 in Acute Stroke Treatment) • a-s-C-o classification of stroke Hemorrhagic stroke By location: • Intracerebral / subarachnoid / intraventricular

• Lobar / deep By etiology: • Primary versus secondary

• Hypertensive hemorrhage

Intracerebral Hemorrhage Classification Ischemic stroke • Harvard Stroke Registry / NINDS Stroke Databank • Oxford Community Stroke Project classification (OCSP) • TOAST (Trial of Org 10172 in Acute Stroke Treatment) • a-s-C-o classification of stroke Hemorrhagic stroke By location: • Intracerebral / subarachnoid / intraventricular

• Lobar / deep By etiology: • Primary versus secondary

• Hypertensive hemorrhage

Intracerebral Hemorrhage Deep versus lobar

Intracerebral Hemorrhage Deep versus lobar 78-year old man Arterial hypertension Dyslipidemia Alcohol abuse Sudden onset left hemiparesis

Intracerebral Hemorrhage Deep versus lobar

Intracerebral Hemorrhage Hemorrhagic infarction

Intracerebral Hemorrhage Deep versus lobar 72-year old man Arterial hypertension Former smoker

Cognitive decline Sudden onset aphasia

Intracerebral Hemorrhage Dural arteriovenous fistula

Intracerebral Hemorrhage Dural arteriovenous fistula

Intracerebral Hemorrhage Classification Ischemic stroke • Harvard Stroke Registry / NINDS Stroke Databank • Oxford Community Stroke Project classification (OCSP) • TOAST (Trial of Org 10172 in Acute Stroke Treatment) • a-s-C-o classification of stroke Hemorrhagic stroke By location: • Intracerebral / subarachnoid / intraventricular

• Lobar / deep By etiology: • Primary versus secondary

• Hypertensive hemorrhage

Intracerebral Hemorrhage Classification Risk Factors Underlying Cause

Brain Hemorrhage

Golden Rules: 1) Every intrecerebral hemorrhage has an underlying cause 2) Risk factors may trigger / modify underlying causes

Intracerebral Hemorrhage Classification Risk Factors Underlying Cause

Brain Hemorrhage

Golden Rules: 1) Every intrecerebral hemorrhage has an underlying cause 2) Risk factors may trigger / modify underlying causes 3) Do not confound causes and risk factors

Intracerebral Hemorrhage Classification Cigarette smoking Carotid Stenosis

embolism

Tabacco infarct… Primary infarct…

Brain Infarction

Intracerebral Hemorrhage Classification Risk Factors [Arterial Hypertension] Underlying Cause

Brain Hemorrhage

[Microangiopathy] Practical Consequence: 1) Visualize underlying cause 2) Search for risk factors 3) Treat causes and/or risk factors, if modifiable…

[deep]

Intracerebral Hemorrhage Classification Risk Factors [Smoking, Alcohol] Underlying Cause

Brain Hemorrhage

[Arterial Aneurysm] Practical Consequence: 1) Visualize underlying cause 2) Search for risk factors 3) Treat causes and/or risk factors, if modifiable…

[+ SAH]

Intracerebral Hemorrhage Classification Risk Factors Underlying Cause

Brain Hemorrhage Do not use:

Primary ICH Hypertensive Hemorrhage

Intracerebral Hemorrhage Classification

Cordonnier C, Al Shahi Salman R, Henon H, von Kummer R, Leys D, Stapf C (in preparation)

Intracerebral Hemorrhage Recent Developments

No dedicated ICH classification…

No standardized ICH diagnostic workup… No specific ICH treatment… Uncertainty regarding preventive intervention for unruptured, hemorrhageprone lesions…

Intracerebral Hemorrhage Diagnosis

3 countries F, NL, UK 3 disciplines NR°, NS, NRO 3 methods

CT, MRI, A° Stroke 2010;41;685-690

Intracerebral Hemorrhage Diagnosis

3 countries F, NL, UK 3 disciplines NR°, NS, NRO 3 methods

CT, MRI, A° Stroke 2010;41;685-690

Intracerebral Hemorrhage Etiological subgroups Moyamoya syndrome / disease

Small vessel disease

• Arteriolosclerosis / lipohyalinosis

Inflammation

• Amyloid angiopathy

• Vasculitis

• Genetic (Col4A1, CADASIL,…)

• Mycotic aneurysm

Vascular Malformation

Malignant disease

• Arteriovenous malformation

• Brain tumor

• Cavernous malformation

• Cerebral metastasis

Intracranial aneurysm

Coagulopathy

Venous disease

• Genetic

• Cerebral sinus / venous thrombosis

• Acquired / iatrogenic

• Dural arteriovenous fistula

Vasoactive drugs

Reversible cerebral vasoconstriction syndrome

Hemorrhagic Infarction Trauma Al Shahi Salman R, Labovitz DL, Stapf C. Br Med J 2009; 339:b2586

Acute intracerebral hemorrhage The (un)usual causes 64-year old woman Arterial hypertension Active smoker

Sudden onset headache followed by coma

Acute intracerebral hemorrhage Aneurysm Rupture

Acute intracerebral hemorrhage The (un)usual causes 58-year old man Aterial hypertension Feeling sick >1 week Admitted: acute confusion Temp 38,2°C CRP 125 mg/dl Cardiac murmur

Acute intracerebral hemorrhage Endocarditis & mycotic aneurysms

Acute intracerebral hemorrhage Endocarditis & mycotic aneurysms Therapeutic Emergency 1) Antibiotics 2) Embolization

3) Valve replacement

Acute intracerebral hemorrhage The (un)usual causes 42-year old woman Thunderclap headache related to sexual activity Improving after 2 hours

Day 1

CT:

normal

LP:

normal

MRI: normal MRA: normal

Acute intracerebral hemorrhage Reversible Cerebral Vasoconstriction Syndrome

Day 1

Day 8

Acute intracerebral hemorrhage Reversible Cerebral Vasoconstriction Syndrome Clinico-radiological Syndrome

1. Several episodes of sudden onset, severe headaches 2. Intracranial vasoconstriction (after >4 days) • Transcranial Doppler

• MRA / CT Angio • Angiography 3. Secondary complications (after 1-14 days)

• Hemorrhagic (ICH, cortical SAH) • Brain infarction 4. Headaches and vasoconstriction resolve within 1 month

Ducros A (2007) Brain 130:3091

Acute intracerebral hemorrhage Reversible Cerebral Vasoconstriction Syndrome

Risik:

• Women • Migraine history

Ducros A (2010) Stroke Ducros A (2007) Brain 130:3091

Acute intracerebral hemorrhage The (un)usual causes 48-year old woman Cigarette smoking Hormonal contraception

Unusual headaches >2 days Sec. generalized seizure Persistent aphasia Right homonymous hemianopia

Acute intracerebral hemorrhage The (un)usual causes

MRV

T2*

Acute intracerebral hemorrhage Cerebral venous thrombosis

HEPARIN!!

MRV

T2*

Acute intracerebral hemorrhage The (un)usual causes

Acute intracerebral hemorrhage Hemorrhagic Infarction

Acute intracerebral hemorrhage Hemorrhagic Infarction

Miller-Fisher C, 2000

Miller-Fisher C, 2000

Acute intracerebral hemorrhage Hemorrhagic Infarction

Acute intracerebral hemorrhage Hemorrhagic Infarction

Acute intracerebral hemorrhage Hemorrhagic Infarction

Acute intracerebral hemorrhage Hemorrhagic Infarction

Intracerebral Hemorrhage Etiological subgroups Moyamoya syndrome / disease

Small vessel disease

• Arteriolosclerosis / lipohyalinosis

Inflammation

• Amyloid angiopathy

• Vasculitis

• Genetic (Col4A1, CADASIL,…)

• Mycotic aneurysm

Vascular Malformation

Malignant disease

• Arteriovenous malformation

• Brain tumor

• Cavernous malformation

• Cerebral metastasis

Intracranial aneurysm

Coagulopathy

Venous disease

• Genetic

• Cerebral sinus / venous thrombosis

• Acquired / iatrogenic

• Dural arteriovenous fistula

Vasoactive drugs

Reversible cerebral vasoconstriction syndrome

Hemorrhagic Infarction Trauma Al Shahi Salman R, Labovitz DL, Stapf C. Br Med J 2009; 339:b2586

Intracerebral Hemorrhage Etiological subgroups Moyamoya syndrome / disease

Small vessel disease

• Arteriolosclerosis / lipohyalinosis

Inflammation

• Amyloid angiopathy • Genetic (Col4A1, CADASIL,…)

Vascular Malformation • Arteriovenous malformation • Cavernous malformation Intracranial aneurysm

• Vasculitis

!

• Mycotic aneurysm

Malignant disease • Brain tumor • Cerebral metastasis Coagulopathy

Venous disease

• Genetic

• Cerebral sinus / venous thrombosis

• Acquired / iatrogenic

• Dural arteriovenous fistula

Vasoactive drugs

Reversible cerebral vasoconstriction syndrome

Hemorrhagic Infarction Trauma Al Shahi Salman R, Labovitz DL, Stapf C. Br Med J 2009; 339:b2586

Intracerebral Hemorrhage Diagnostic Work-up

Intracerebral Hemorrhage Diagnostic Work-up CT scan

CT angio MRI/MRA

Angiogram

Intracerebral Hemorrhage Diagnostic Work-up CT scan

Hem detection Acute f-up

ICH, SAH, IVH Volume

CT angio

Arterial/venous

MRI/MRA

Hem detection

find: Aneurysm, spot sign search: AVM, sinus thrombosis find: SWD, ven. thrombosis, hem infarction, CCM search: AVM, DAVF, RCVS, moya, aneurysm find: Aneurysm, AVM, DAVF, moya, RCVS search: Vasculitis find: Vasculitis, tumor, CAA

Angiogram Vascular imaging

Biopsy

Brain/meninges

Intracerebral Hemorrhage Diagnostic Work-up CT scan

N=152 prospective patients

N=67 (44%) women Mean age: 63 years (SD +/-12)

CT angio MRI/MRA

Angiogram

Intracerebral Hemorrhage Diagnostic Work-up CT scan

N=152 prospective patients

N=2

Small vessel disease

N=2

Sinus thrombosis

N=73

Small vessel disease

N=9

Hemorrhagic infarcts

N=4

Cavernous malformation

N=3

Acute RCVS

N=3

Venous thrombosis

N=2

Brain tumor

N=4

DAVF / AVM

N=2

Aneurysms

21% acutely

N=2

Moya-moya

treatment relevant

N=1

Acute RCVS

CT angio MRI/MRA

Angiogram

3%

63%

6% 72%

Intracerebral Hemorrhage Diagnostic Work-up CT scan

Ancillary studies: normal (blood lab, retina, LP, genetics, …)

CT angio

Repeat imaging after 3 - 4 months MRI/MRA

Angiogram

imaging negative

Diagnosis (?!)

Intracerebral Hemorrhage 2-step diagnosis

Initial MRI: cortical hematoma

Angiography: normal

Intracerebral Hemorrhage Arteriovenous Malformation

3-month follow-up MRI: negative

3-month follow-up angiography showing L MCA AVM

Intracerebral Hemorrhage Arteriovenous Malformation

Embolization: AVM occlusion

Intracerebral Hemorrhage 2-step diagnosis

♀ 37 years, left internuclear ophtalmoplegia, ataxia, dissociated sensory deficit

Intracerebral Hemorrhage Cerebral Cavernous Malformation

T1 & gadolinium

T2*

Intracerebral Hemorrhage Recent Developments: Diagnostic Workup

Intracerebral Hemorrhage Recent Developments: Diagnostic Workup Every ICH has an underlying etiology - Rule: there is only secondary ICH - Avoid: “primary ICH”, “hypertensive ICH”, …

Intracerebral Hemorrhage Recent Developments: Diagnostic Workup Every ICH has an underlying etiology Add imaging modalities until you visualize the cause - Brain imaging (CT, MRI)

- Vascular imaging (CT-A, MRA) - Acute MRI/MRA soon to be diagnostic standard

Intracerebral Hemorrhage Recent Developments: Diagnostic Workup Every ICH has an underlying etiology Add imaging modalities until you visualize the cause Some causes require acute treatment decisions

- Arterial disease: aneurysm, hem infarction, … - Venous disease: thrombosis, DAVF, …

- Systemic disease: endocarditis, vasculitis, …

Intracerebral Hemorrhage Recent Developments: Diagnostic Workup Every ICH has an underlying etiology Add imaging modalities until you visualize the cause Some causes require acute treatment decisions

All causes have long-term treatment implications - Remove focal lesion, if possible: Aneurysm, AVM, CCM, DAVF, … - Treat risk factors (hypertension, smoking, …)

Intracerebral Hemorrhage Recent Developments: Diagnostic Workup

Intracerebral Hemorrhage Recent Developments: Diagnostic Workup

Intracerebral Hemorrhage Recent Developments

No dedicated ICH classification…

No standardized ICH diagnostic workup… No specific ICH treatment… Uncertainty regarding preventive intervention for unruptured, hemorrhageprone lesions…

Intracerebral Hemorrhage Etiological subgroups = Therapeutic Subgroups Moyamoya syndrome / disease

Small vessel disease

• Arteriolosclerosis / lipohyalinosis

Inflammation

• Amyloid angiopathy

• Vasculitis

• Genetic (Col4A1, CADASIL,…)

• Mycotic aneurysm

Vascular Malformation

Malignant disease

• Arteriovenous malformation

• Brain tumor

• Cavernous malformation

• Cerebral metastasis

Intracranial aneurysm

Coagulopathy

Venous disease

• Genetic

• Cerebral sinus / venous thrombosis

• Acquired / iatrogenic

• Dural arteriovenous fistula

Vasoactive drugs

Reversible cerebral vasoconstriction syndrome

Hemorrhagic Infarction Trauma Al Shahi Salman R, Labovitz DL, Stapf C. Br Med J 2009; 339:b2586

Intracerebral Hemorrhage Etiological subgroups = Therapeutic Subgroups Moyamoya syndrome / disease

Small vessel disease

• Arteriolosclerosis / lipohyalinosis

Inflammation

• Amyloid angiopathy

• Vasculitis

• Genetic (Col4A1, CADASIL,…)

• Mycotic aneurysm

Vascular Malformation

Malignant disease

• Arteriovenous malformation

• Brain tumor

• Cavernous malformation

• Cerebral metastasis

Intracranial aneurysm

Coagulopathy

Venous disease

• Genetic

• Cerebral sinus / venous thrombosis

• Acquired / iatrogenic

• Dural arteriovenous fistula

Vasoactive drugs

Reversible cerebral vasoconstriction syndrome

Hemorrhagic Infarction Trauma Al Shahi Salman R, Labovitz DL, Stapf C. Br Med J 2009; 339:b2586

Acute intracerebral hemorrhage Acquired small vessel disease

Acute intracerebral hemorrhage Acquired small vessel disease

Progression (24h)

Volume increase (mass effect) Ventricular extension Hydrocephalus Intracranial pressure Brain stem compression

Acute intracerebral hemorrhage Acquired small vessel disease Brain CT (with contrast):

Brain CT

Angio-CT

Post contrast CT

« Spot – Sign » Wada R, et al. Stroke 2007;38:1257-1262

6h control CT

Acute intracerebral hemorrhage Acquired small vessel disease

Prospective, multicenter N=268, age >18

ICH < 6hrs,

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