Idea Transcript
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,