Cerebral Microbleeds (CMB)

Cortical cerebral microbleeds (CMBs) on SWI sequence
INTRACEREBRAL HEMORRHAGE

Cerebral microbleeds

David Goldemund M.D.
Updated on 11/03/2024, published on 02/03/2024

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 Definition

  • cerebral microbleeds (CMBs) or cerebral microhemorrhages are characterized by hemosiderin deposits caused by small hemorrhages, and may serve as a radiologic biomarker of small vessel disease (SVD)
    • black lesions on blood-sensitive MRI sequences (GRE T2* or SWI images)
  • often found incidentally; the prevalence increases with age
    • general population ∼ 10-15%   (Sveinbjornsdottir, 2008)
    • 6.5% of the individuals aged 45-50 years
    • up to 40% of the population > 80 years    [Poels, 2009]
    • incidence of CMBs in AD is 20-43%; in vascular dementia, it is up to 85%!   [Seo, 2007]
  • microhemorrhages are associated with:
    • older age (prevalence increasing significantly after the age of 75)
    • hypertension
    • smoking
    • white matter disease and lacunar stroke
    • previous ischemic stroke or intracerebral hemorrhage (ICH)
    • COVID-19 leukoencephalopathy (mostly in critically ill patients) (Agarwal, 2020)
  • a high number of microbleeds is associated with an increased risk of:

  • increased risk of progression is common in:

Cerebral microbleeds and the risk of hemorrhage

  • the risk of ICH increases with the number of CMBs
    • ≥ 5 CMBs – OR for ICH 2.8
    • ≥ 10 CMBs – OR for ICH 5.5!
  • according to the CROMIS-2 trial, the risk of bleeding in patients with CMBs is 9.8/1000 vs. 2.6/1000 patient-years (adjusted hazard ratio 3·67, 95% CI 1·27–10·60) [Wilson, 2018]
  • the incidence of ICH is up to 5%/year in cases with multiple lobar CMBs [Van Etten, 2014]

Classification

  • subcortical (mainly caused by arteriolopathy)  → Binswanger’s disease
  • cortical (mostly caused by CAA – with an increased risk of lobar hemorrhage)
  • combined (combination of CAA and arteriolosclerosis or rather arteriolosclerosis alone) [Jung, 2020]

Radiographic features of hypertensive angiopathy

  • cerebral microbleeds (predominantly in the deep grey nuclei and brainstem)
  • subcortical infarcts (lacunar) in the deep grey nuclei, white matter, and brainstem
  • dilated perivascular spaces in the basal ganglia
  • white matter hyperintensities and hyperintensities in the deep grey nuclei and brainstem on T2

Diagnostic evaluation

  • detectable only on specific sequences, such as gradient-recalled echo (GRE) and susceptibility-weighted imaging (SWI)
    • microbleeds are inapparent on other MRI sequences and CT
  • black, round, or oval lesions that are 2-5 mm in diameter, associated with a blooming artifact, which overestimates the size of the lesions

Greenberg’s criteria (Roob, 1999)

  • black round or ovoid lesion with blooming on GRE/SWI
  • devoid of signal hyperintensity on T1- or T2-weighted sequences
  • at least half surrounded by brain parenchyma
  • distinct from other potential mimics such as iron/calcium deposits, bone, or vessel flow voids
  • clinical history, excluding traumatic diffuse axonal injury

Blooming artifact

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Use GRE or SWI sequence?

  • both techniques are used to detect blood products and calcifications due to their sensitivity to local susceptibility effects
  • T2*-weighted gradient-echo (GRE) sequences operate in 2D multi-slice mode, using relatively long TR’s, low flip angles, and relatively long TE’s
  • modern susceptibility-weighted imaging (SWI) methods are based on GRE sequences but include numerous enhancements for improved differentiation between paramagnetic (hemorrhage) and diamagnetic (calcification) substances
  • SWI is superior to GRE (particularly in the diagnosis of traumatic brain injury and microvascular angiopathy)
  • however, SWI sequences take longer than standard GRE and are more susceptible to motion artifacts
Microbleeds

Cerebral amyloid angiopathy (CAA) on GRE

Cortical cerebral microbleeds and lobar hematomas in patient with cerebral amyloid angiopathy
Cortical cerebral microbleeds (CMBs)
Cortical cerebral microbleeds (CMBs) on SWI sequence

Differential diagnosis

  • calcium and iron deposits (calcium is hyperdense on the CT scan)   PKAN “eye-of-the-tiger” - bilateral central hyperintense areas within a hypointense region in the medial globus pallidus (T2 a GRE)  PKAN “eye-of-the-tiger” - bilateral central hyperintense areas within a hypointense region in the medial globus pallidus (T2)
    • diseases with an accumulation of iron  see here
  • flow void from veins or small arteries on the cross-section  Subcortical CMB and artery cross section (green arrow)
    • follow the continuum of the vessel on adjacent slices
  • cavernous malformation (cavernoma)  Cerebral cavernous malformation with a typical popcorn appearance
  • malignant melanoma metastases   The malignant melanoma
    • T1 – hyperintense (due to bleeding and/or the presence of melanin)
    • T2 – hypointense
    • T1 C+ – diffuse or ring-like saturation
    • T2*- hypointense
  • pneumocephalus and gas embolism
  • metallic emboli from mechanical heart valve (very rare)

Management

  • no specific therapy
  • strict treatment of hypertension
  • careful indication and monitoring of anticoagulant (preferably use DOACs) and antiplatelet therapy (avoid DAPT if possible)
  • the risk of symptomatic intracranial hemorrhage (sICH) may increase after thrombolytic therapy in patients with cerebral microbleeds (CMBs)
  • CMBs < 10  ⇒  IVT seems safe (ESO guidelines 2021) (AHA/ASA 2019 IIa/B-NR)
  • CMBs > 10 ⇒ IVT carries a higher risk of ICH; the expected benefit of treatment must outweigh the risk ⇒ consider IVT in patients with a severe stroke (ESO guidelines 2021)
    • a small study retrospectively found a slightly increased risk (3%) of bleeding in patients with microbleeds on GRE [Fiehler, 2007]
    • an increased risk of bleeding is associated with CAA as a cause of microbleeds
  • no MRI screening is recommended to assess CMB burden before making a treatment decision regarding IVT (ESO guidelines 2021)
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  • no definitive guidelines exist for antiplatelet use in patients with CMBs
  • single antiplatelet therapy – seems a safe and beneficial approach (RESTART trial subanalysis) [Salman, 2019]
  • dual antiplatelet therapy (DAPT) – individual risk-benefit analysis is crucial (DAPT is acceptable after recent stenting, etc.)

Carotid-cavernous fistula (CCF)

Direct CCF with rapid filling of ophtalmic veins on DSA

INTRACEREBRAL HEMORRHAGE / VASCULAR MALFORMATIONS

Carotid cavernous fistula (CCF)

David Goldemund M.D.
Updated on 11/03/2024, published on 01/02/2024

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  • carotid cavernous fistula is a specific variant of arteriovenous fistula (→ DAVF) – it is defined as a pathological communication between the cavernous sinus (CS) and the internal carotid artery (ICA) or its branches (from either the ICA or the ECA or both)
  • CCF can occur spontaneously or as a result of trauma
  • the cavernous sinus is a venous plexus that receives drainage from the sphenoparietal sinus, superior ophthalmic vein (SOV), inferior ophthalmic vein (IOV), superior petrosal sinus (SPS), inferior petrosal sinus (IPS), and basilar venous plexus → anatomy of cerebral veins and dural sinuses

Classification

  • the Barrow classification is the most widely used system to categorize CCFs
  • type A is usually of traumatic etiology with the classic triad of clinical symptoms (tinnitus, pulsatile exophthalmos, and conjunctival chemosis)
  • indirect CCFs (C-D) are usually of spontaneous origin with milder clinical presentation
Etiology
  • traumatic (75%)
  • spontaneous (intracavernous aneurysm, vasculopathies such as Ehlers-Danlos or FMD)
Hemodynamic classification
  • high-flow
  • low-flow
Anatomy (type A-D) – the Barrow classification
  • direct (type A)
    Type A – direct communication between ICA and cavernous sinus (CS)
  • indirect, dural (type B-D)
    Type B – fistula is fed by ICA branches 
    Type C – fistula is fed by ECA branches Barrow C type CCF fed from ECA branches (DSA) 
    Type D – fistula is fed by both ICA and ECA branches
CCF classification according to Barrow (type A-D)

Clinical presentation

These symptoms are usually fully expressed in type A, whereas the findings are more subtle in indirect types (often only retrobulbar pain, diffuse headache, or conjunctival hyperemia)

  • pulsatile or persistent exophthalmos (proptosis)
    • ipsilateral (up to 75%)
    • bilateral (up to 1/3 of cases)
    • contralateral to CCF
  • pulsatile tinnitus (mostly synchronous with the heartbeat) + murmur audible in the forehead, synchronous with a heartbeat and disappearing after compression of the carotid artery 
  • painful ophthalmoparesis with diplopia (symptoms may fluctuate) [Li, 2019]
  • ipsilateral amaurosis
  • ipsilateral or bilateral conjunctival chemosis
  • dilated subcutaneous periorbital veins
  • papilledema
  • hemorrhagic complications (2%) – SAH, ICH, epistaxis
Ocular manifestations of CCF

Diagnostic evaluation

  • brain CT/MRI
    • CT/MRI does not show the fistula itself
    • helps rule out other orbital or intracranial expansive lesions
    • it may show enlargement of the cavernous sinus, ophthalmic veins, and oculomotor muscles Enlarged ophtalmic vein (orange arrow) and oculomotor muscles on the affected side 
    • in the case of trauma,  CT in the bone window should rule out skull base fracture
  • vascular imaging
    • CTA/MRA   Direct CCF (Type A) on MRA  Indirect carotid-cavernous fistula (CCF) type B on CT angiography. The red arrow shows early filling of the right cavernous sinus
      • ideal for initial diagnosis
      • normal results do not 100% exclude carotid-cavernous fistula; DSA should be performed if CCF is suspected
    • DSA  Barrow C type CCF fed from ECA branches (DSA)
      • the essential imaging modality
      • shows the size and location of the fistula, assesses its hemodynamic impact and venous drainage
  • ophthalmologic examination   Cystoid macular edema and ischemic retinopathy in indirect CCF
    • visual assessment
    • fundoscopy – detection of vascular changes (dilated veins with potential hemorrhage) and papilledema
Direct carotid-cavernous fistula (CCF) type A on CT angiography

Differential diagnosis

  • tumors compressing the cavernous sinus (e.g., pituitary adenomas, craniopharyngiomas)
  • endocrine orbitopathies Endocrine orbitopathy on MRI
    • without significant chemosis and increased fundus vascular filling
  • cavernous sinus thrombosis
  • retrobulbar orbital expansive process
  • cluster headache

Management

  • endovascular embolization techniques (either transarterial or transvenous) are the preferred
  • tinnitus typically disappears immediately following a successful procedure
  • eye symptoms resolve gradually over weeks to months

Direct fistula (type A)

Endovascular treatment

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Neurosurgery

  • open surgery or radiosurgery are used as second-line or adjuvant therapeutic options, typically after the prior failure of endovascular procedures

Indirect fistula (type B-D)

  • it is recommended to monitor the patient with low-flow fistulas and mild symptoms, as the spontaneous resolution of symptoms due to fistula thrombosis is not uncommon
  • the effect of repeated external carotid compression under ultrasound guidance has been reported   [Higashida, 1986] [Goldemund, 2006)
  • endovascular treatment is suggested in more severe cases and those with clinical progression (visual deterioration, malignant exophthalmos, and chemosis)
    • coiling of the feeding artery
    • transvenous cavernous sinus coiling
Embolization of feeding artery (CCF Barrow type C)

Cerebral amyloid angiopathy-related inflammation

Cerebral amyloid angiopathy-related inflammation
INTRACEREBRAL HEMORRHAGE

Cerebral amyloid angiopathy-related inflammation

David Goldemund M.D.
Updated on 27/01/2024, published on 22/01/2024

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  • cerebral amyloid angiopathy (CAA) is a common small vessel disease characterized by the deposition of amyloid β (Aβ) protein mainly in the media and adventitia of small- and medium-sized leptomeningeal and cortical blood vessels
  • Cerebral Amyloid Angiopathy-Related Inflammation (CAA-RI) is a relatively rare and aggressive variant of CAA with characteristic radiological findings (extensive, asymmetric vasogenic edema)
  • because corticosteroids and immunosuppressive therapy can be effective, early diagnosis and treatment are crucial

Definition and etiopathogenesis

  • two subtypes of CAA-RI are now recognized:
    • inflammatory CAA (ICAA) – non-destructive perivascular inflammation
    • amyloid β-related angiitis (ABRA) – transmural or intramural inflammation
  • these two conditions cannot be differentiated based on imaging alone and share the same clinical manifestations and prognosis. These diseases probably constitute a spectrum from CAA to PACNS
  • some other synonyms can be found in the literature, such as primary angiitis of the central nervous system associated with cerebral amyloid angiopathy, cerebral amyloid angiitis, or cerebral amyloid inflammatory vasculopathy

Clinical Presentation

  • no significant gender difference
  • usually older individuals (an average age of 67 at diagnosis – younger than with non-inflammatory CAA)
  • clinical course
    • acute or subacute, less typically chronic
  • at least one of the following clinical features is required and should not be attributable to acute ICH
    • headache
    • altered level of consciousness
    • behavioral or cognitive changes (decline)
    • focal neurological deficits
    • seizures
    • hallucinations

Diagnostic evaluation

Neuroimaging

  • parenchymal imaging
    • CT – subcortical WML lesions – usually a solitary area of low density
    • MRI
      • T2-FLAIR – extensive asymmetric confluent white matter hyperintensities representing vasogenic edema; asymmetry should not be due to past intracerebral hemorrhage
        •  symmetric WMLs meet the criteria for “possible” CAA-RI
      • SWI/GRE (SWI is better)
  • vascular imaging (MRA, CTA)
    • in ABRA, multifocal stenoses with wall thickening/enhancement in medium-sized arteries have been observed
    • angiography is unremarkable in ICAA
  • vessel wall imaging (dark blood MRI)
    • vessel wall enhancement is not specific to inflammation and may be seen in non-inflammatory amyloid angiopathy
Cerebral amyloid angiopathy-related inflammation

Serologic and cerebrospinal fluid (CSF) tests

  • elevation of inflammatory biomarkers has been observed (CRP, ESR in 30-60% of cases)
  • APOE ε4/ε4 homozygosity is significantly correlated with CAA-RI
    • 76.9% of CAA-RI patients versus 5.1% in non-inflammatory CAA
    • APOE ε4 probably increases Aβ deposition, has a pro-inflammatory effect, and increases the risk of vascular disease
    • cases of CAA-RI patients with APOE ε2/ε2 and APOE ε2/ε3 genotypes have also been reported
  • CSF analysis
    • increased CSF protein
    • pleocytosis (in 60% of cases)
    • typically, no oligoclonal bands are detected
    • anti-Aβ autoantibodies are elevated in the acute phase
    • patients with CAA-RI have relatively low levels of Aβ42 and Aβ40 in the CSF

Biopsy

  • the gold standard for diagnosis is autopsy or brain biopsy
  • brain biopsy should be taken from an area with abnormal radiologic manifestations
  • however, negative brain biopsy findings do not exclude the diagnosis of CAA-RI because of the segmental distribution of pathological changes

Diagnostic criteria

  • the definitive diagnosis of CAA-RI requires histopathological confirmation
  • as biopsy is invasive and carries certain risks, criteria for the diagnosis of CAA-RI have been established based on clinical and radiological data (Chung, 2009)  (Auriel, 2016) 
  • patients with probable CAA-RI can be treated with immunosuppressive therapy empirically to avoid brain biopsy
  • if there is no response to corticosteroids within 3 weeks, biopsy should be reconsidered to confirm the diagnosis
  • age ≥40 years
  • at least one of these clinical features not directly attributable to an acute ICH:
    • headache
    • decrease in consciousness
    • behavioral change
    • focal neurological signs and seizures
  • MRI with white matter hyperintensities (unifocal or multifocal, corticosubcortical or deep) that extend to subcortical white matter
  • at least one of these hemorrhagic lesions:
  • absence of neoplastic, infectious, or other cause
Probable diagnosis
  • the same criteria as the possible category, only MRI white matter hyperintensities asymmetry is not due to past intracerebral hemorrhage
Definite diagnosis
  • positive biopsy or autopsy

Differential diagnosis

  • Amyloid-related imaging abnormalities (ARIA reported in AD patients treated with amyloid-lowering therapies
    • monoclonal antibodies bapineuzumab, solanezumab, and aducanumab
    • usually only incidental findings on imaging or edema-related symptoms (headaches, vomiting, confusion)
    • edema is related to the breakdown of the blood-brain barrier and may typically resolve over a few months
    • treatment: withhold further treatment with the amyloid-lowering agent + start steroids
  • infection
    • progressive multifocal leukoencephalopathy (PML)
    • meningoencephalitis of various causes
    • neurosarcoidosis
  • acute disseminated encephalomyelitis (ADEM)
  • primary CNS vasculitis
    • PACNS usually occurs in younger patients (mean age, 45 years), while CAA-RI is common in older individuals
    • PACNS is a more likely diagnosis when symptoms involve the spinal cord
    • multiple intracranial stenoses in small and mid-size vessels
  • posterior reversible encephalopathy syndrome (PRES)
    • similar bilateral confluent T2 WMLs, often associated with hypertension or other conditions
    • usually negative GRE/SWI
    • sometimes difficult to distinguish from CCA-RI; it may be necessary to observe changes during follow-up to make the correct diagnosis (⇒ progressive lesions on SWI in CAA-RI)
  • neoplasms, such as metastases or lymphomas

Management

  • spontaneous remissions have been documented, but the overall prognosis for most untreated patients is typically unfavorable
  • high-dose corticosteroids (+/- additional immunosuppressive therapy) can improve symptoms and imaging abnormalities
    • both approaches seem to have similar outcomes  (Caldas, 2015)
    • clinical improvement occurs within 1 or 2 weeks, followed by a regression of the inflammatory findings on MRI
    • immunosuppressants may be considered in cases that do not respond adequately to glucocorticoids or to prevent relapse
    • one study has shown that more patients with ABRA (33.0%) require a combination of steroids and immunosuppressants compared to patients with ICAA (12.8%) to achieve similar results (Chu, 2016)
  • the most commonly used immunosuppressants include:
    • cyclophosphamide
    • azathioprine
    • mycophenolate mofetil
    • methotrexate
    • immunoglobulin
  • there is limited empirical data regarding the selection of medication, optimal dose, and duration of treatment; dosage regimens may be extrapolated from the management of other autoimmune diseases
  • non-responders (~ 60%) progress to severe disability or death despite treatment
  • relapse may occur after steroid withdrawal or during the tapering process; steroid therapy remains effective during recurrence; however, an increased presence of microbleeds may be observed on GRE/SWI sequences
  • although tumors, neurosarcoidosis, Hashimoto encephalopathy, ADEM, or PACNS are unlikely to be aggravated by empirical corticosteroid use, treatment may obscure the accurate diagnosis of these conditions
  • moreover, before initiating immunosuppressive treatment, it is crucial to rule out underlying infections

Diagnosis of intracerebral hemorrhage

Blend sign (baseline and 3hr later)

INTRACEREBRAL HEMORRHAGE

Diagnosis of intracerebral hemorrhage

David Goldemund M.D.
Updated on 07/03/2024, published on 27/11/2023

[toc]

  • for patients presenting with stroke-like symptoms, rapid neuroimaging using CT or MRI is recommended to confirm the diagnosis of spontaneous intracerebral hemorrhage (ICH)
  • the detection of intracerebral bleeding itself by imaging methods is easy; the diagnostic evaluation is focused on determining the underlying etiology

Physical Examination and focused history

  • time of symptoms onset (or time patient was last seen normal)
  • symptoms
    • headache
      • thunderclap: aneurysm, RCVS, rarely CVST
      • slower onset: mass lesion, CVST, ischemic stroke with hemorrhagic transformation
    • focal neurologic deficits
    • seizures
    • decreased level of consciousness
  • vascular risk factors
    • prior ICH or SAH
    • hypertension
    • hyperlipidemia
    • diabetes
    • metabolic syndrome
    • imaging biomarkers (e.g., cerebral microbleeds)
  • medications
    • anticoagulant drugs
    • thrombolytic drugs
    • antiplatelet agents
    • NSAIDs
    • vasoconstrictors (associated with RCVS): triptans, SSRIs, decongestants, stimulants, phentermine, sympathomimetics
    • antihypertensives (as a marker of chronic hypertension)
    • estrogen-containing oral contraceptives (↑risk of CVST)
  • cognitive impairment or dementia (possible amyloid angiopathy)
  • substance use
    • smoking
    • alcohol use
    • marijuana (associated with RCVS)
    • sympathomimetic drugs (amphetamines, methamphetamines, cocaine)
  • liver disease, uremia, malignancy, and hematologic disorders (→ secondary coagulopathy)

Computed tomography (CT)

Non-contrast CT scan (NCCT)

  • baseline examination objectives:
    • detect and localize the hematoma
    • assess its type, volume, probable etiology, risk of complications
    • assess the prognosis (→ ICH scales)
  • fresh blood is hyperdense on NCCT   Density of an acute hematoma on NCCT
    • increased density is caused by the high hemoglobin content of retracted clot or sedimented blood
    • the density of the hematoma in the acute stage is typically around 70-80HU; if the lesion has a density > 100-120HU, , it is likely to be calcification, foreign body, etc. Densities of acute hematoma and calcification in plexus
    • resorption of the hematoma occurs within days to weeks; accompanied by a decrease in its density
    • hematoma becomes isodense within 1-6 weeks
    • in the chronic stage, a hypodense pseudocyst with atrophy of the surrounding brain tissue is usually found at the site of the resorbed hematoma (indistinguishable from old ischemia) Chronic intracerebral hemorrhage on NCCT
  • vasogenic edema gradually appears around the subacute hematoma as a hypodense area  ICH with collateral edema on NCCT Edema surrounding hemorrhage
  • type and location of bleeding:
    • typical “hypertensive” bleeding   Typical bleeding localisation in patiens with hypertension 
      • putamen, thalamus, internal capsule (lenticulostriate arteries)   Lenticulostriatal arteries
      • brainstem, cerebellum
      • concomitant hypertension + age > 55 (65) years almost rule out other etiologies
    • atypical bleeding → search for structural cause (CTA/MRI+MRA/DSA)
      • lobar hematomas  Repeated lobar hematomas in patient with CAA
      • primary intraventricular hemorrhage (IVH) – exclude AVM or small aneurysm in the ventricular wall or SAH from AComA with perforation of the terminal lamina and bleeding into the third ventricle   Primary intraventricular hemorrhage (IVH)
      • age < 50 years in the absence of hypertension despite typical ICH location
      • large and early vasogenic edema
Thalamic hemorrhage

Hemorrhage in the basal ganglia

Cerebellar hemorrhage

Pontine hemorrhage

Intraventricular hemorrhage (hemocephalus)

Lobar hematoma with the island sign

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CT angiography (CTA)

  • CTA (+/- venography) is useful for the identification of the potential source of bleeding (vascular malformations) or cerebral venous thrombosis
  • it can be performed as part of the baseline CT scan in patients with:
    • age < 50 years
    • atypical hematoma location/appearance
    • hematoma in typical location without history of hypertension
    • isolated intraventricular hemorrhage
  • in atypical parenchymal hematomas, add MRI+MRA or DSA if baseline CTA is negative
    • it may be reasonable to start with MRI and MRA to establish a non-macrovascular cause of ICH (such as CAA, deep perforating vasculopathy, cavernous malformation, or malignancy)
    • MRI may help to rule out the hemorrhagic transformation of ischemia
  • search for markers of hemorrhage expansion
    • spot sign on source CTA images or post-contrast CT images Spot sign on CTA Spot sign on CTA (top), progression of IC hematoma in the same patient (bottom) Spot sign on CTA
    • “leakage sign” may also serve as a predictor of continued bleeding   Leakage sign on CTA  [Orito, 2016]
      • initial CTA + delayed phase (5 min interval)
      • a 10% increase in HU density indicates ongoing bleeding

Magnetic resonance imaging (MRI)

  • MRI of the brain is highly sensitive for detecting intracerebral hemorrhage
  • the appearance of hemorrhage depends on the stage of hemoglobin breakdown (see table below)
    • oxy-Hb is weakly diamagnetic, deoxy-Hb has 4 unpaired electrons per iron atom and is strongly paramagnetic
  • gradient recalled echo (GRE) can detect early bleeding with similar sensitivity to NCCT ⇒  MRI can be used as the initial imaging method in stroke programs (Kidwell, 2004)     → see here
    • hyperacute hematoma:
      • T1 isointense
      • T2/FLAIR – isointense or slightly hyperintense
      • GRE hypointense (initially only hypointense rim + core of heterogenous signal intensity due to the diamagnetic oxyhemoglobin
      • DWI hyperintense, ADC hypointense
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Digital subtraction angiography (DSA)

  • indicated in search for the source of bleeding (consider patients’ age, clinical condition, comorbidities, prognosis, the location and extent of bleeding)
  • DSA is often replaced by CTA/MRA, which can be performed quickly and without significant risk as part of the initial diagnostic workup
  • DSA should be performed if CTA/MRA suggests a macrovascular cause of bleeding  (AHA/ASA guidelines 2022, 1/C-LD)
    • DSA confirms the diagnosis of a malformation and provides additional information about the main tributaries, presence, type, and extent of the nidus, type of flow (high or low flow), venous drainage, and other features (stenosis of a draining vein,  intranidal or perinidal aneurysm, etc.)
  • DSA is performed when CTA/MRA is negative or equivocal, and there is a reasonable suspicion of a bleeding source  Cerebral arteriovenous malformation (DSA)
  • in patients with spontaneous ICH and a negative DSA and no clear microvascular diagnosis or other structural lesions, it may be reasonable to repeat DSA 3-6 months after ICH to identify a previously obscured vascular lesion

Other examinations and tests

Blood tests

  • complete blood count (check platelets)
    • admission anemia is associated with hemorrhagic expansion and poor outcome
    • thrombocytopenia is associated with increased mortality
  • coagulation tests  (to exclude anticoagulant-related hemorrhage and coagulopathy from other causes)
    • APTT, Quick, INR, TT, fibrinogen (especially after thrombolysis)
    • ECT and Hemoclot (dabigatran) 
    • specific anti-Xa (xabans)
  • glucose
    • admission hyperglycemia is associated with unfavorable short- and long-term outcome
  • urea nitrogen, osmolality
  • liver tests (coagulopathy secondary to liver failure)
  • ionogram including Ca2+, Mg2+
  • creatinine/estimated glomerular filtration rate (GFR)
    • renal failure on admission is associated with poor functional outcome
    • possible altered clearance of DOACs
  • D-dimers
  • cardiac enzymes + troponin
  • inflammatory markers (ESR, CRP) – infective endocarditis?
  • urine toxicology screen (sympathomimetic drugs are associated with ICH)
  • pregnancy test in a woman of childbearing potential (exclude peripartum angiopathy, eclampsia, HELLP syndrome, and cerebral sinus thrombosis)

Others

  • 12-lead ECG on admission, followed by continuous ECG monitoring
  • pulse oximetry
  • blood pressure monitoring (invasive/noninvasive)
  • chest x-ray

Cerebral venous angioma (DVA)

Venous angioma (Developmental venous anomaly)

INTRACEREBRAL HEMORRHAGE / VASCULAR MALFORMATIONS

Cerebral venous angioma (DVA)

David Goldemund M.D.
Updated on 11/03/2024, published on 20/09/2023

[toc]

  • cerebral venous angioma, also known as Developmental Venous Anomaly (DVA), is a congenital malformation where dilated veins with no abnormal feeding artery (caput medusae sign) converge into a single large abnormal draining vein
  • DVAs rarely bleed  ⇒ if a hemorrhage is present, look for associated cavernous malformation (15-20%), AVM, or a tumor
  • most commonly, DVAs are localized in the parietal and frontal lobes (up to 64%) and cerebellum (up to 30%)
Venous angioma (Developmental venous anomaly)

Clinical presentation

  • commonly asymptomatic (usually an incidental finding on neuroimaging)
  • epileptic seizures
  • headaches
  • venous infarction (in case of rare thrombosis of the draining vein)
  • intracerebral bleeding is rare (0.2-0.4% per year)

Diagnostic evaluation

Venous angioma (DVA)

Venous angioma

Venous angioma on CTA

Differential diagnosis

Management

  • a conservative approach is common for isolated DVA
  • the draining vein often serves as drainage for the surrounding unaffected areas
    • surgical occlusion or spontaneous thrombosis may lead to venous infarction
  • if needed, treat concurrent malformations

FAQs

  • a benign cerebral vascular malformation in which dilated veins converge into a single large draining vein
  • there is no abnormal feeding artery
  • adjacent brain parenchyma is normal
  • DVAs are considered congenital
  • DVA is primarily diagnosed by MRI or CT angiography
  • SWI is the preferred MRI sequence to detect venous malformations
  • generally asymptomatic (typically incidental finding on neuroimaging)
  • symptoms, if present, are usually secondary to associated lesions (CCM, AVM)
  • thrombosis of the draining vein is an extremely rare complication leading to venous infarction
  • AVM has large feeding arteries, tortuous vessels, and abnormal adjacent brain parenchyma that are not observed in DVAs
  • seizures may occur in the presence of an associated epileptogenic lesion (e.g., cavernoma or dysplasia) or as a result of complications (e.g., venous infarction)
  • typically, no intervention is needed unless associated with other vascular malformations (AVM, cavernous malformation) or symptomatic hemorrhage
  • surgical intervention is rarely indicated and generally not recommended due to the role DVAs play in venous drainage
  • excellent, particularly when isolated; there is no increased risk of bleeding in isolated DVAs
  • typically, routine follow-up is not required unless DVA is associated with other vascular anomalies

Management of intracerebral hemorrhage

Repeated lobar hematomas in patient with CAA
INTRACEREBRAL HEMORRHAGE

Management of intracerebral hemorrhage

David Goldemund M.D.
Updated on 27/03/2024, published on 20/08/2023

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The INTERACT3 trial (2023) showed that timely administration of a care bundle that included early intensive lowering of systolic blood pressure, strict glucose control, treatment of fever, and rapid reversal of abnormal coagulation resulted in reduced disability, lower mortality rates, and better overall quality of life

General therapy

The tabs below discuss specific issues related to the conservative treatment of ICH. Otherwise, general principles of acute stroke management and intensive care, including management of intracranial hypertension, apply.

Prognosis
  • assess the extent and characteristics of ICH on baseline CT scan
    • high ICH score is associated with poor prognosis
    • spot sign predicts ICH progression
  • asses neurological deficits, age, comorbidities, and biological status
  • assess ICH etiology (SMASH-U)
  • start intensive therapy for the first 24-48hours, then consider whether to continue or switch to DNR (AHA/ASA 2015 IIa/B)
    • involve family members in decision-making
Care setting

according to AHA/ASA guidelines 2022

  • start care in a specialized unit (e.g., stroke unit) with a multidisciplinary team providing the full range of high-acuity care and expertise
    • patients with clinical signs of evolving hydrocephalus should be transferred to centers with neurosurgical capabilities for definitive management (e.g., EVD placement and monitoring)
    • it is reasonable to provide care in a neuro-specific ICU rather than a general ICU for patients with moderate-to-severe spontaneous ICH, IVH, hydrocephalus, or infratentorial bleeding
    • patients with IVH or infratentorial bleeding should be transferred to centers with neurosurgical capabilities
  • using standardized protocols and/or order sets is recommended to reduce disability/mortality
  • frequent neurological assessment is reasonable for up to 72 hours after admission to detect early neurological deterioration
VTE prevention

→ prevention of VTE in stroke patients

  • start intermittent pneumatic compression (IPC) on the admission day, if possible  (AHA/ASA 2022 1/B-R)
  • after bleeding has ceased and coagulation is normal, consider starting enoxaparin 0.4 mL SC 1-0-0 (low-dose LMWH) 24-48 hours after the onset of ICH (AHA/ASA 2022  2b/C-LD)
  • a retrievable IVC filter should be considered for patients with pulmonary embolism (PE) or acute deep vein thrombosis (DVT) AHA/ASA 2022 2a/C-LD)
    • a medical device that is temporarily implanted into the inferior vena cava (IVC) to prevent life-threatening pulmonary embolism in patients with contraindications to full anticoagulation
    • delaying treatment with UFH or LMWH for 1-2 weeks after the onset of ICH might be considered  (AHA/ASA 2022 2b/C-LD)
  • graduated compression knee-high or thigh-high length stockings alone are not beneficial for VTE prophylaxis
Statins
  • do not discontinue statin therapy
    • continuation of prior statin treatment appears to be safe
    • patients already using statins have a better outcome and lower mortality  [Flint, 2014]
  • do not start statin therapy in the acute phase of ICH due to the increased risk of perihemorrhagic edema [Sprügel, 2021]
  • statins can be safely started later if necessary
Strict glucose and fever control

Strict glycemia and fever control according to INTERACT3 trial

  • no diabetes: target 6.1-7.8 mmol/L  (109-140 mg/dL)
  • diabetes: target  7.8-10.0 mmol/L  (140-180 mg/dL)
  • target body temperature ≤ 37.5° C
Intracranial hypertension

→ more about intracranial hypertension here

  • it is important to maintain intracranial pressure (ICP) and cerebral perfusion pressure (CPP) within normal ranges to reduce the risk of secondary brain injury
  • the head should be elevated to reduce ICP and maintain adequate CPP (15-45°)
  • sedation
  • indication for ICP monitoring in ICH is ambiguous
    • consider in patients with GCS ≤ 8 with extensive hematoma, intraventricular bleeding, or hydrocephalus (AHA/ASA 2022 IIb/B-NR)
  • if ICP is monitored, start treatment at ICP 20-25 mmHg
    • target ICP < 20mm Hg, target CPP 50-70mmHg
    • bolus hyperosmolar therapy ( MANNITOL or hypertonic saline) → more here
  • the efficacy of early prophylactic hyperosmolar therapy to improve outcome is not well established (AHA/ASA 2022 2b/B-NR)
  • corticosteroids should not be used!  (AHA/ASA 2022 III/B-R)
ASM
  • anti-seizure medications (ASMs) are not recommended for prophylaxis (even in lobar hematomas, which are associated with a higher risk of seizures) (AHA/ASA 2022 3/B-NR)
  • patients with seizures should be treated with ASM to reduce their morbidity → follow protocol for the treatment of symptomatic seizures  (AHA/ASA 2022 1/C-LD)
  • in patients with unexplained abnormal or fluctuating mental status or suspected seizures, continuous EEG monitoring (24 hours) is reasonable to diagnose electrographic seizures and epileptiform discharges  (AHA/ASA 2022 2a/C-LD)
Physiotherapy
  • start rehabilitation early (24-48 h after onset) in patients with mild to moderate ICH who are hemodynamically stable
    • training of activities of daily living (ADL), stretching, functional task training
    • focus on support of circulatory and respiratory functions and prevention of DVT and pressure ulcers (bed sores)
  • the timing of verticalization should be based on individual assessment and should start > 24 hours after onset, taking into account factors such as the severity of the hemorrhage, neurological deficit, and overall clinical status of the patient
    • early mobilization and verticalization can help prevent complications, such as pneumonia, deep vein thrombosis, and pressure ulcers
  • in patients with spontaneous ICH, very early and intense mobilization (incl. verticalization) within the first 24 hours may be harmful (AVERT trial)   (AHA/ASA guidelines 2022

Blood pressure management in the acute stage

  • on admission, check BP every 5-10 minutes or start invasive BP monitoring
  • aggressive and rapid treatment of hypertension is an essential therapeutic approach (along with correction of coagulopathy)
    • high BP is associated with an increased risk of hematoma progression with worse clinical outcome
    • initiating treatment within 2 hours of ICH onset and achieving the target within 1 hour may be useful to reduce the risk of hematoma expansion and improve functional outcome (AHA/ASA 2022, 2a/C-LD)
    • ischemia around the hematoma plays a minor role (except perhaps in large hematomas), and BP reduction seems safe
  • continue with chronic PO medications if possible; if dysphagia or decreased LOC is present, use parenteral therapy or place a nasogastric (NG) tube
  • in patients with known hypertension, the target BP may be higher due to altered autoregulation with the risk of decreased CPP
  • nitroprusside is not recommended due to its potential to increase intracranial pressure (ICP)
  • smooth and sustained control of BP is required; avoid sudden drops or peaks in BP and maintain Mean Arterial Pressure (MAP) >85 mm Hg
  • if the ICP is monitored, then correct BP to maintain CPP 60-80 mm Hg
Initial systolic blood pressure (SBP) 150-220 mm Hg in patients with ICH of mild-to-moderate severity
  • target SBP ≤ 140 mm Hg (ESO guidelines 2021)  (AHA/ASA 2022 2b/B-R)
    • lowering SBP to 140 mm Hg is safe and may reduce hematoma expansion and lead to improved outcomes
    • maintain in the range of 130-150 mm Hg
    • target <140 mm Hg was used in the INTERACT3 trial
  • no significant clinical benefit of lowering < 140 mmHg was demonstrated
    • In the INTERACT2  trial, there were fewer patients with mRS 3-6 in the intensive treatment group (SBP<140 mm Hg) compared with the standard treatment group (SBP <180 mm Hg);  the difference was not statistically significant
    • the benefit of lowering SBP <140 mm Hg was not demonstrated in the ATACH-2 trial – lowering SBP <120 mm Hg may even be harmful
  • acute lowering of SBP to <130 mm Hg is potentially harmful (AHA/ASA 2022 3/B-R)
  • start antihypertensive treatment ASAP (ideally within 2 hours of symptom onset)
  • the reduction of SBP should not exceed 90 mm Hg from baseline values  (ESO guidelines 2021)

    • greater BP reduction was significantly associated with acute kidney injury regardless of preexisting CKD  (Burgess, 2018)
Initial SBP > 220 mmHg or large hematoma
  • limited data on the safety and efficacy of a target SBP ≤ 140 mm Hg
  • SBP reduction should not exceed 90 mmHg from the baseline
  • cautious BP lowering is required in these patients ⇒  maintain CPP > 6070 mm Hg
  • the 1st line of IV drugs:
    • urapidil (EBRANTIL)
    • enalapril (ENAP)
    • labetalol (TRANDATE)
  • if they fail, try nitrates – isosorbide dinitrate (ISOKET)
  • start peroral medication ASAP (e.g., via NG tube if necessary) and gradually reduce/withdraw parenteral medication

Correction of hemostasis disorders

  • early detection and urgent correction of coagulopathy is a key procedure in ICH therapy
  • antifibrinolytic agents are not recommended except for thrombolysis-related bleeding

Patients with normal coagulation parameters

  • the FAST trial with recombinant f.VII (NOVOSEVEN) failed to show a reduction in mortality and disability. Mayer, 2008]
    • reduced hematoma growth was offset by an increased risk of thromboembolic complications (especially in the 80 μg dose cohort)  (AHA/ASA 2010 class III, LoE A)
  • similarly, the effect of etamsylate (DICYNONE) and tranexamic acid (EXACYL) has not been demonstrated
    • negative TICH-2 and STOP-AUST  trials
    • negative meta-analysis of 4 RCTs  – hemostatic therapy showed a marginally significant benefit in reducing hematoma expansion in high-risk patients (predicted by CT scan markers). However, no significant improvement in functional outcome or reduction of mortality was observed [Nie, 2021]
    • the TICH-2  trial showed no benefit in the subgroup of patients with positive spot sign   [Ovesen, 2021]

Intracerebral hemorrhage in thrombocytopenia and thrombocytopathy

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Hemorrhagic infarction, thrombolysis-related bleeding

→ bleeding complications during thrombolysis

  • usually a consequence of late reperfusion with extravasation of blood into infarcted tissue (0.6-5%)
  • risk factors:
    • early anticoagulation (therefore not recommended)
    • thrombolysis (symptomatic IC bleeding ~ 6%)
    • extensive infarction
    • large artery occlusion with late recanalization
    • poorly controlled hypertension and hyperglycemia
  • clinical presentation depends on the extent of bleeding (ECASS classification)
Hemorrhage classification after stroke/reperfusion (ECASS II)

Intracerebral hemorrhage during anticoagulation therapy

  • prolonged bleeding on anticoagulant therapy is present in ~ 36-54% of patients (warfarin > DOAC) ⇒ neutralization of the anticoagulant effect is therefore essential [Steiner, 2017]

Surgical treatment

  • the goals of surgery are to:
    • decrease ICP
    • reduce the secondary damage from edema
    • reduce the risk of herniation
    • eliminate potential sources of bleeding

Monitoring of intracranial pressure (ICP)

  • ICP sensor can be implanted after correction of coagulation parameters
  • indications are equivocal
    • patients with GCS ≤ 8 with extensive parenchymal hematoma, intraventricular hemorrhage with obstructive hydrocephalus (AHA/ASA 2015 IIb/C)
  • intraparenchymal or intraventricular sensor
    • the intraventricular catheter is inserted through the brain into the lateral ventricle; it allows concurrent CSF drainage
  • major risks:
    • bleeding – the type of the hemorrhage depends on the site of insertion (intraparenchymal, intraventricular, or subdural)
    • infection (up to 12%, the risk is higher with intraventricular catheters) – CSF should be sent for cytology and culture analysis if infection is suspected
  • leave the sensor for a maximum of 5-7 days; beyond this time, the risk of infection increases, and the accuracy of the measurement decreases
  • manage ICP according to head trauma protocols
    • target CPP 50-70 mmHg
    • target ICP < 20 mmHg

External ventricular drainage (EVD)

  • typically used for massive intraventricular hemorrhage or expanding cerebellar hematoma with acute obstructive hydrocephalus (AHA/ASA 2022 I/B-NR)
    • modern catheters allow concurrent ICP monitoring
    • careful monitoring of consciousness and repeated CT scans are required

Hematoma evacuation

  • relieving the pressure of the hematoma on the surrounding tissue may reduce secondary damage
  • craniotomy is associated with complications, including continued bleeding
    • the benefit of surgery is unknown (AHA-ASA 2015 IIb/A)
    • the STICH and STICH III trials showed no benefit of standard surgery over conservative management (< 48h, lobar hematomas 10-100mL, no IVH)
  • minimally invasive surgery seems to be beneficial
    • positive results of ENRICH trial with minimally invasive parafascicular surgery (MIPS) may change current practice
      • age 18-80 years, ICH volume 30 – 80 mL, GCS 5-14, premorbid mRS 0-1,  intervention initiated within 24 hours after the onset of stroke symptoms
  • urgent evacuation of ICH (< 4h) does not improve outcome or mortality and may increase the risk of bleeding (AHA/ASA 2015 IIb/A)
Indications

Surgery (12-96h from onset) indicated

  • supratentorial hematoma with volume of ~ 30-60mL, localized near the brain surface + progressive alteration of LOC due to expansive hematoma
  • cerebellar hematoma > 3cm (> 10-15 mL) or brainstem compression with/without obstructive hydrocephalus
    • prompt surgical evacuation of hemorrhage with or without EVD is recommended over medical management alone to reduce mortality  (AHA/ASA 2022 I/B-R)
    • simple insertion of a ventricular catheter without simultaneous hematoma evacuation is not recommended (AHA/ASA 2015 III/C)
  • ICH evacuation may be combined with treatment of the source of bleeding
    • especially acute treatment of aneurysms is required (high risk of early rebleeding)

Surgery not indicated

  • deep subcortical hematomas with volume ≥ 60mL and GCS ≤ 8
    • high mortality ~80-90%; results of conservative and surgical treatment do not differ according to the STICH trial
  • hematoma in supratentorial localization with volume < 30mL
  • brainstem hematoma
  • cerebellar hematoma < 3 cm in diameter without brainstem compression/hydrocephalus
  • urgent surgery< 4 hours from onset of bleeding
Surgical procedures
  • MIS (minimally invasive surgery) – stereotactic hematoma evacuation (with/without tPA application)  (AHA/ASA 2022 2a/B-R)
    • 12-72 h from the onset, GCS 5-12
    • hematoma volume > 20-30mL
    • puncture and aspiration of hematoma to reduce the volume to < 10-15 mL, possible tPA application of 1mg every 8h or 2mg every 12h
    • favorable results in phase 2 trial (mortality 7% vs. 14%) – MISTIE (Minimally Invasive Stereotactic Surgery – rt-PA for ICH Evacuation)
    • preliminary results of the phase 3 MISTIE III trial are negative (primary outcome mRS 0-3/year 45% vs. 41%); however, there appears to be a clinical effect with residual hematoma volume < 15 ml
    • positive results of the ENRICH trial
    • prefer MIS over craniotomy evacuation (AHA/ASA 2022)
  • osteoplastic craniotomy with hematoma evacuation or with decompressive craniectomy
    • in most patients, the usefulness of craniotomy for hemorrhage evacuation to improve functional outcomes or mortality is uncertain (AHA/ASA 2022 class 2b/A)
    • in patients with supratentorial ICH who are deteriorating, craniotomy for hematoma evacuation might be considered a lifesaving procedure  (AHA/ASA 2022 class 2b/C-LD)
  • decompressive craniectomy (with or without hematoma evacuation) can be a lifesaving procedure in comatose patients with prominent mass effect (with midline shift) and drug-refractory IC hypertension (AHA/ASA 2022 2b/C-LD)
    • the effectiveness of decompressive craniectomy with or without hematoma evacuation to improve functional outcomes is uncertain

Treatment of the source of bleeding

  • the source of bleeding is most common in atypically localized hematomas and younger patients without hypertension
  • acute intervention is indicated for aneurysms with an extremely high risk of early rebleeding
  • acute management of other bleeding sources follows the general indications for surgery:
    • mostly expansive hematoma, 30-60 mL, GCS > 8
    • cerebellar hematoma compressing the brainstem (usually > 3 cm)
  • malformations are often complicated and require a multidisciplinary approach (a combination of endovascular, surgical, and radiotherapy)

Surgery in intraventricular hemorrhage (IVH)

  • treat the underlying cause of bleeding
  • detect and treat possible obstructive hydrocephalus (serial neurological status examinations and repeated CT scans are required for the diagnosis)
    • external ventricular drainage (EVD) may reduce mortality, especially in patients with large ICH/IVH and impaired level of consciousness (LOC) (AHA/ASA 2022 1/B-NR)
      • for patients with a GCS score >3 and primary IVH or secondary IVH (with supratentorial ICH of <30-mL volume) requiring EVD, minimally invasive IVH evacuation with EVD plus thrombolytics is safe and reasonable compared with EVD alone to reduce mortality (AHA/ASA 2022 2a/B-NR)
      • for patients with a GCS score >3 and primary IVH or secondary IVH (with supratentorial ICH of <30-mL volume) requiring EVD, the effectiveness of minimally invasive IVH evacuation with EVD plus the use of thrombolytics to improve functional outcomes is uncertain
      • for patients with large ICH/IVH and impaired LOC, the efficacy of EVD to improve functional outcome is not well-established
    • intraventricular application of tPA may facilitate the thrombus evacuation from the ventricles; it appears safe, but clinical efficacy is unclear
      • CLEAR-IVH study – systemic bleeding 4%, ventriculitis 2%
      • CLEAR III trial – no substantial improvement in functional outcome at mRS 3 cutoff compared to saline irrigation; mortality reduced by 10%
        • intraventricular tPA protocol – 1 mg of alteplase, 8h apart; up to 12 doses
    • alternative procedures:  endoscopic evacuation of the hematoma with ventriculostomy, VP shunt, or lumbar drainage – benefit is unclear (AHA/ASA 2022 2b/C-LD)

Cerebral cavernous malformation

Cerebral cavernous malformation - popcorn appearance
INTRACEREBRAL HEMORRHAGE / VASCULAR MALFORMATIONS

Cerebral cavernous malformation

David Goldemund M.D.
Updated on 22/03/2024, published on 20/06/2023

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Definiton

  • cerebral cavernous malformation (CCM) is a well-circumscribed accumulation of dilated, thin-walled vessels that affect the brain
    • only a layer of endothelium and subendothelial stroma is present; smooth muscle cells and elastic fibers are absent
    • the pathogenesis of CM remains unclear
  • forms:
    • sporadic
      • incidence in the population 0.4-0.9% [Sage, 1993]
      • accounts for 8-15% of all vascular malformations
      • usually one lesion (in about 70% of cases)
    • familial
      • a genetically linked multiple cavernomatosis (AD)  Multiple cerebral cavernomatosis (SWI)
      • often symptomatic
      • possible de novo CM formation
  • can be localized anywhere (approximately 80% are supratentorial)
  • CM-associated anomalies:
MRI 0.25-0.7%
rebleeding 4.5%
MRI, DSA 0.2-0.4%
DSA, CTA 2-4 %
rebleeding 6-18%
MRI very low
DSA, MRA, CTA
type I – very low
type II, III – up to 8%
Carotido-cavernous fistula (CCF) DSA, MRA very low
Vascular malformations
  • familial cases of CCM have autosomal dominant (AD) inheritance with incomplete penetrance
  • account for 10–50% of all cases
  • mutations have been identified in three genes:
    • KRIT1 (Krev interaction trapped 1) on 7q21-q22 (CCM1)
    • MGC4067 (Malcavernin) on 7p13 (CCM2)
    • PDCD10 (programmed cell death 10) on 3q26-q27 (CCM3)
  • genotype–phenotype correlations between the three forms are emerging
    • CCM1 mutation carriers appear to have a milder hemorrhage phenotype but may present with more seizures and extraneurologic manifestations
    • CCM3 patients may have a more aggressive clinical course with an earlier age of onset of symptoms and greater risk of ICH
Cavernous malformation

Pathophysiology

  • erythrocyte diapedesis through the pathological cavernoma wall
    • hemoglobin degradation products induce pathological excitability, oxidative damage, and gliosis, leading to epilepsy
  • bleeding into the cavernoma ⇒ ↑ malformation volume
  • bleeding into the surrounding area

Clinical presentation

  • asymptomatic in up to 44% of cases
  • epileptic seizures (45-70%) [Májovský, 2014] [Sage, 1993]
    • mostly associated with lesions localized in the frontal and temporal lobes
    • cavernous malformations account for approximately 4% of refractory epilepsy
  • bleeding
    • low risk (0.25-0.7% per year), increased after prior bleeding episodes  (⇒ 4.5% / year)
    • higher risk with infratentorial lesions
    • hemorrhages are generally non-fatal due to low pressure within the malformation; however, repeated hemorrhages may ultimately lead to severe neurological deficit
  • headache (20-30%)
  • focal neurological deficit (e.g., in case of cerebellar or brainstem lesion)
  • risk factors for adverse outcome
    • multiple lesions
    • presence of CCM3 genotype
    • early clinical presentation
    • infratentorial localization
    • lesion diameter >1 cm
    • associated developmental venous anomaly (DVA)

Diagnostic evaluation

  • CT
    • lesion is typically poorly visible (negative CT in up to 50% of cases)
    • cavernous malformation may appear slightly hyperdense, with small calcifications   Slightly hyperdense cavernous malformation on NCCT   Cavernous malformation
    • minimal or absent postcontrast enhancement Cavernous malformation with a subtle enhancement on contrast-enhanced CT
    • no mass effect or collateral edema
    • recent bleeding may be detected
  • MRI (sensitivity 100%) Cavernous malformation  
    • characteristic popcorn appearance   Cavernous malformation with a characteristic popcorn appearance
    • heterogeneous lesion with a hemosiderin rim (T2-hypointense) Large cavernous malformation with hemosiderin rim 
    • prominent finding on GRE – “blooming artifact”
    • slight enhancement is possible  [Pinker, 2006]
  • DSA is normal
Cavernous malformation (FLAIR)

Appearance of the cavernous malformation on different imaging modalities
Cavernous malformation
Multiple cavernous malformations (MRI SWAN)
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  • the Zabramski MRI classification has been proposed for the classification of cerebral cavernous malformations
  • primarily useful for scientific purposes
  • type I: subacute hemorrhage
    • T1: hyperintense
    • T2: hypo-/hyperintense
  • type II:  classic “popcorn” lesion  Cavernous malformation - popcorn appearance
    • T1 and T2: mixed-signal intensity centrally
    • T2*/GRE/SWI: hypointense rim with blooming
  • type III: chronic hemorrhage
    • T1: hypointense/isointense centrally
    • T2: hypointense centrally
    • T2*/GRE/SWI: hypointense rim with blooming
  • type IV: multiple punctate microhemorrhages
    • GRE/SWI: “black dots” with blooming
    • difficult to distinguish from small capillary telangiectasias

Management

Surgery and radiotherapy

  • microsurgical resection
    • relatively safe procedure with low morbidity and mortality  [Májovský, 2014]
    • proven indications:
      • refractory epilepsy (up to 90% of patients are seizure-free after the surgery)
      • recurrent bleeding
    • in infratentorial CMs, surgery is preferred in cerebellar lesions and hemorrhagic lesions localized near the ventricle or cistern  [Amato, 2013]
  • stereotactic radiosurgery (SRS) may be considered for inoperable lesions [Liščák, 2013] [Liščák, 2000]
    • indications and therapy results are controversial
    • in contrast to AVMs, the direct effect of therapy is not immediately observable; the long-term clinical course may differ from that of untreated lesions

Conservative therapy and follow-up

  • follow-up MRI is recommended every 1-2 years for asymptomatic lesions
  • keep blood pressure in the normal range
  • beta-blockers may reduce the risk of intracranial hemorrhage or persistent/progressive focal neurological deficit in patients with CCM   (Zuurbier, 2022)

Max-ICH score

ICH volume in mL (cm3) ≈ A (cm) x B x C /2. Volume is 4.4 mL

ADD-ONS / SCALES

Max-ICH score

David Goldemund M.D.
Updated on 29/08/2023, published on 08/06/2022

  • simple, reliable tool for predicting unfavorable long-term (12-month) functional outcome and mortality after intracerebral hemorrhage (ICH)
  • ICH involving both lobar and non-lobar regions should be scored based on the location where the ICH most likely originated
  • if 2 large ICHs occur simultaneously, more than 1 point referring to the ICH volume should be assigned
  • the maximum total score for a single hematoma (with/without IVH) is 9 points
  • each 1-point increase in the max-ICH score was associated with an OR of 1.24 for an unfavorable outcome  (Suo, 2018)
  • external validation comparing the ICH score and the max-ICH score shows a similar prognostic value (Schmidt, 2018)
Max-ICH score (0-9 points for a single ICH)
0-6
7-13
14-20
≥21
0
1
2
3
Age (years)
≤ 69
70-74
75-79
≥ 80
0
1
2
3
Lobar hematoma volume ≥ 30 mL
1
Non-lobar hematoma volume ≥ 10 mL
1
Intraventricular hemorrhage (IVH)
1
Oral anticoagulants
1
Max-ICH score and outcome (Suo, 2018)
Calculation of hematoma volume
volume in mL (cm3) ≈ A x B x C /2 (round or ellipsoid shape)
volume in mL (cm3) ≈ A x B x C /3 (irregular, separated, or multinodular shape) [Huttner, 2006]
A, B –  hemorrhage width and length – see image  (in cm)
C = height
  • number of CT slices showing hematoma x CT slice thickness
  • measure the height on sagittal reconstruction (2D tools in TOMOCON or other software)

For more precise measurement, count slices as follows:

  • slice with ≥75% area of hemorrhage counts as one slice
  • slice with 25-75% area of hemorrhage counts as 0.5 slices
  • slice with <25% counts as zero slices
ICH volume in mL (cm3) ≈ A (cm) x B x C /2. Volume is 4.4 mL

Intraventricular hemorrhage in adults

Obstructive hydrocephalus following IVH

INTRACEREBRAL HEMORRHAGE

Intraventricular hemorrhage in adults

David Goldemund M.D.
Updated on 06/11/2023, published on 22/04/2022

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Introduction

  • intraventricular hemorrhage (IVH), also known as hemocephalus, is characterized by the presence of blood within the cerebral ventricular system
  • initially, IVH is present in one-quarter of patients with intracerebral hemorrhage (ICH) but may occur later as an extension of the ICH
    • patients with larger hematomas, or those with hemorrhages in the caudate nuclei or thalamic locations, are more likely to bleed into the ventricles
  • IVH significantly increases the risk of obstructive hydrocephalus, which in turn increases morbidity and mortality
  • an important determinant of the outcome is the volume of the intraventricular hemorrhage
Primary intraventricular hemorrhages
  • the cerebral ventricular system consists of four interconnected cavities known as cerebral ventricles. Each ventricle contains a choroid plexus responsible for the production of cerebrospinal fluid (CSF). The ventricular system continues from the fourth ventricle into the central canal of the spinal cord
  • ventricles and the central canal of the spinal cord are lined with ependymal cells, a specialized epithelium connected by tight junctions. These junctions form the blood-cerebrospinal fluid barrier
Cerebral ventricles

Classification and etiology

Primary IVH

  • blood in the ventricles with little or no blood in the parenchyma   Intraventricular hemorrhage (hemocephalus)
  • possible causes:
    • vascular malformations (AVM, subependymal cavernous malformation, aneurysm)
    • coagulopathy  Primary intraventricular hemorrhage caused by warfarin overdose
    • intraventricular tumors (ependymoma, the choroid plexus metastases)
    • hypertensive bleeding

Secondary IVH

  • more frequent
  • a significant extraventricular component (either parenchymal or subarachnoid) is present with secondary expansion to the ventricles
    • propagation of intracerebral hematoma Secondary IVH from ICH in basal ganglia and thalamus  Secondary IVH from the thalamic bleeding  Secondary intraventricular hemorrhage
    • SAH (beware of possible reflux from the spinal SAH)
    • trauma (Ravi, 2019)

Clinical presentation

  • in primary IVH, symptoms resemble those of SAH (sudden and severe headache and meningeal syndrome)  → clinical presentation of SAH
  • in secondary IVH, signs and symptoms predominantly arise from the primary parenchymal lesion
  • extensive hemorrhages may lead to an altered level of consciousness, accompanied by cardiorespiratory compromise

Diagnostic evaluation

Non-contrast CT scan (NCCT)

  • the primary imaging technique for patients with acute stroke symptoms or sudden headache
  • blood within the ventricles is hyperdense and usually best visualized in the occipital horns
  • follow-up CT scans should be performed to exclude acute obstructive hydrocephalus  Obstructive hydrocephalus following IVH

Intraventricular hemorrhage (hemocephalus)

MRI

  • MRI is sensitive to small amounts of blood, especially in the posterior fossa (CT may be inconclusive due to artifacts)
    • FLAIR – signal intensity is time-dependent. Blood appears hyperintense in the first 48 hours; after that, the signal becomes more variable (exclude flow artifacts)
    • GRE, or preferably SWI  – detects even small amounts of blood in the occipital horns (characterized by a hypointense rim)
Intraventricular hemorrhage on MRI

Vascular imaging (CTA, MRA, DSA)

  • rule out vascular malformations, moyamoya, etc.

Management

  • treat the underlying cause of bleeding
  • detect and treat possible obstructive hydrocephalus (serial neurological status examinations and repeated CT scans are required for the diagnosis)
    • external ventricular drainage (EVD) may reduce mortality, especially in patients with large ICH/IVH and impaired level of consciousness (LOC) (AHA/ASA 2022 1/B-NR)
      • for patients with a GCS score >3 and primary IVH or secondary IVH (with supratentorial ICH of <30-mL volume) requiring EVD, minimally invasive IVH evacuation with EVD plus thrombolytics is safe and reasonable compared with EVD alone to reduce mortality (AHA/ASA 2022 2a/B-NR)
      • for patients with a GCS score >3 and primary IVH or secondary IVH (with supratentorial ICH of <30-mL volume) requiring EVD, the effectiveness of minimally invasive IVH evacuation with EVD plus the use of thrombolytics to improve functional outcomes is uncertain
      • for patients with large ICH/IVH and impaired LOC, the efficacy of EVD to improve functional outcome is not well-established
    • intraventricular application of tPA may facilitate the thrombus evacuation from the ventricles; it appears safe, but clinical efficacy is unclear
      • CLEAR-IVH study – systemic bleeding 4%, ventriculitis 2%
      • CLEAR III trial – no substantial improvement in functional outcome at mRS 3 cutoff compared to saline irrigation; mortality reduced by 10%
        • intraventricular tPA protocol – 1 mg of alteplase, 8h apart; up to 12 doses
    • alternative procedures:  endoscopic evacuation of the hematoma with ventriculostomy, VP shunt, or lumbar drainage – benefit is unclear (AHA/ASA 2022 2b/C-LD)

Blend Sign

Blend sign - a mix of hyperdense and relatively hypodense areas (difference > 18 HU) easily distinguishable by eye

Blend sign

David Goldemund M.D.
Updated on 21/03/2024, published on 25/02/2022

  • early hematoma growth is observed in approximately one-third of the patients with spontaneous intracerebral hemorrhage (ICH)
  • the blend sign (BS) on baseline non-contrast computed tomography (NCCT) is a marker of increased risk of hemorrhage progression and a predictor of poor outcome in patients with ICH  Blend sign predicts poor prognosis in ICH patients (Li, 2017)   [Li, 2017]
    • blend sign is not associated with poor outcomes in patients with hypertensive ICH after stereotactic minimally invasive surgery (sMIS)  (Yang, 2021)
  • the blend sign has a good correlation with the spot sign, the latter being more sensitive and reliable, but it requires the administration of a contrast agent  [Sporns, 2017]
  • blend sign and black hole sign can help predict outcome when CT angiography is unavailable
Blend sign specifications
  • a mix of hyperdense and relatively hypodense areas (difference > 18 HU)
  • easily distinguishable by eye
  • sharply demarcated from each other
  • the hypodense area is not completely surrounded by the hyperdense area
Blend sign - a mix of hyperdense and relatively hypodense areas (difference > 18 HU) easily distinguishable by eye
Blend sign
Blend sign (baseline and 3hr later)

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