Secondary Intraparenchymal Hemorrhages

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Chapter 11 Secondary Intraparenchymal Hemorrhages

Alejandro A. Rabinstein, Steven J. Resnick

Multiple causes other than hypertension may provoke intraparenchymal hematomas. Recognizing them may be difficult, especially in the acute phase. However, some of these causes must be promptly identified to avoid devastating complications. Hemorrhages induced by excessive anticoagulation and those produced by bleeding vascular anomalies are examples of highly dangerous situations that demand immediate therapeutic intervention.

The patient’s history may offer clues to unveil the source of bleeding. Patients with amyloid angiopathy often manifest signs of cognitive deterioration preceding their first clinical hemorrhage. Patients and relatives must be probed to investigate whether there is any history of substance abuse or consumption of sympathomimetic drugs (decongestants, appetite suppressants). Previous episodes of bleeding in other sites may indicate an underlying hemorrhagic diathesis, and previous thromboembolic events should raise suspicion of cerebral venous thrombosis. History of cancer favors the possibility of brain metastasis, whereas recurrent cerebral hemorrhage may be a sign of amyloid angiopathy, untreated vascular anomalies, or coagulopathy. Any recent history of recent head trauma may be significant and should be noted. Fevers or preexistent debilitating systemic illness may be manifestations of infectious endocarditis.

Certain physical signs can also provide helpful information. Examination should specifically focus on searching for external signs of head trauma (raccoon’s eyes, Battle’s sign in the mastoid area), fever, cardiac murmur and other features of endocarditis (subungual splinter hemorrhages, petechiae, splenomegaly, Roth spots, Janeway lesions, Osler’s nodes), lymphadenopathy, peripheral tracks of venous puncture (suggesting intravenous drug use), and exaggerated skin bruises (possibly disclosing bleeding diathesis). Blood studies must include a complete cell count, platelet count, prothrombin time, activated partial thromboplastin time, liver enzymes, and urine drug screen.

Brain imaging is particularly valuable in the distinction of secondary causes of intraparenchymal hematoma (Table 11-1). Radiological hints are frequently subtle but quite reliable. Imaging often provides the first, and sometimes only evidence that a secondary cause is responsible for the hemorrhage. Throughout this chapter we attempt to summarize useful discriminating signs as we present examples of the most common secondary causes of intraparenchymal bleeding.

TABLE 11-1 Secondary causes of intraparenchymal hemorrhage

Cerebral amyloid angiopathy

Hemorrhagic transformation of ischemic infarction

Anticoagulation

Thrombolysis

Intrinsic coagulation disorders

Sympathomimetic drugs (cocaine, amphetamines, decongestants, anorectics)

Infective endocarditis

Vasculitis

Moyamoya disease

Neurosurgical and neuroendovascular procedures

Cerebral venous thrombosis

Vascular anomalies

Saccular aneurysms

Arteriovenous malformations

Cavernous malformations

Dural arteriovenous fistulas

Tumors (primary or metastatic)

Head trauma

CEREBRAL AMYLOID ANGIOPATHY

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid β and other amyloidogenic peptides in the walls of medium and small cortical and leptomeningeal vessels leading to vascular fragility and probably dysfunction.^1,² Amyloid deposition and hemorrhage are favored by the presence of APOE 2 and 4 alleles,³ and vascular amyloid deposits are often (but not always) seen in combination with changes of Alzheimer’s disease.⁴ The restricted location of the deposits explains why hemorrhages are always lobar and involve the cortex of the brain (or, much less commonly, the cerebellum). It may account for more than one third of cases of lobar intracerebral hemorrhage (ICH) in the elderly population (age > 65 years).^5,⁶ The prevalence of CAA in brain-bank studies exceeds 50% in patients over age 70,⁷ and it is severe in more than 10% of patients over age 80.⁸ Thus the incidence of CAA-related hemorrhages is likely to continue to increase substantially with the aging of the population.

The definitive diagnosis of CAA requires pathological demonstration. However, in practice this is rarely feasible or justified. Criteria have been designed to make the diagnosis of possible or probable CAA based solely on clinical and radiological data.⁹ Possible CAA requires CT or MRI evidence of a single lobar ICH in a patient 55 years or older with no other cause for the hemorrhage. When there is clinicoradiological evidence of two or more lobar cerebral or cerebellar hemorrhages in a patient 55 years or older with no other causes for the lesions the diagnosis is probable CAA.

These criteria focus on the identification of cases of lobar ICH that can only be attributed to CAA. However, CAA may also play a role in the genesis of lobar hematomas in patients with coexistent causes. In fact, it has been shown that CAA increases the risk of intracranial bleeding in patients receiving anticoagulants ¹⁰ and thrombolytic agents.¹¹

The diagnosis of CAA is relying increasingly on the use of MRI, particularly gradient-recall echo sequences. This is well illustrated in the following case vignette and elaborated in the subsequent teaching points.

Case Vignette

A 73-year-old man without previous known illnesses was brought to the emergency department by his son for evaluation of acute speech changes. On physical examination, the patient was fully awake and had fluent dysphasia without associated motor or sensory deficits. Head CT scan disclosed a left parietal hemorrhage of moderate volume (Figure 11-1). When specifically questioned, the patient’s son acknowledged that he had noticed subtle changes in the behavior of his father over the previous year. His memory had been declining for a longer time. Brain magnetic resonance imaging (MRI) revealed multiple cortical microhemorrhages, supporting the clinical suspicion of cerebral amyloid angiopathy. The patient developed episodes of agitation during the hospitalization and only achieved minimal recovery from his dysphasia.

Figure 11-1 Computed tomography scan of the head shows a left parietal hemorrhage ascribed to amyloid angiopathy (upper row). Note characteristic lobar location and heterogeneity, likely caused by bleeding in stages. On brain magnetic resonance imaging, the hematoma has mixed hyperintense and isointense signals on the T1-weighted sequence (middle row, left) and it is predominantly hypointense on the T2-weighted sequence (middle row, right), reflecting the acute to early subacute nature of the hemorrhage. Gradient-recall echo sequence demonstrates multiple other areas of cortical microhemorrhage (lower row), a distinctive feature of amyloid angiopathy.

♦ Lobar hemorrhages related to CAA may have variable sizes. Symptomatic hematomas are often voluminous, but most lesions are small and asymptomatic.

♦ Symptomatic hematomas often have heterogeneous appearance, suggesting that bleeding may occur in more than one temporal phase. The clinical correlate of this observation is the presentation with deficits that often have progressed over hours, unlike those accompanying hypertensive hemorrhages or ischemic strokes.

♦ CAA-related hemorrhages have a predilection for the temporal and occipital lobes.¹² The reasons for this spatial clustering in the posterior aspects of the brain remain speculative.

♦ Lobar ICH from CAA has an elevated rate of recurrence (as high as 14% per year in patients at highest risk based on their apolipoprotein E genotype)³ (Figure 11-2).

♦ Gradient-recall echo has excellent sensitivity for the detection of lobar microhemorrhages. Identification of these small asymptomatic lesions is highly supportive of the diagnosis of CAA in an elderly patient with lobar hemorrhage (Figure 11-3).

♦ The total burden of microhemorrhages on MRI predicts the risk of recurrent symptomatic lobar transpose.¹³

♦ On MRI scan, patients with CAA and lobar hemorrhage(s) often exhibit signs of concomitant extensive white matter damage. This combination of lesions suggests more widespread vascular dysfunction and is associated with cognitive impairment ¹⁴ (Figure 11-3).

Figure 11-2 A 74-year-old man with progressive decline and recent hemorrhage causing left leg weakness (2–3 weeks earlier) was transferred for evaluation of recurrent lobar hematoma producing confusion, right hemiparesis, and partial neglect. Brain magnetic resonance imaging is shown in the upper row. It discloses a relatively small right frontal parasagittal hemorrhage hyperintense on T1-weighted sequence (left) and with hyperintense core surrounded by hypointense rim on gradient-recall echo (GRE) (right), consistent with a late subacute hematoma. In addition, it also reveals a larger right parietal hemorrhage which is isointense on T1-weighted sequence and predominantly hypointense (with some areas of increased signal intensity) on GRE, reflecting the acuteness of this lesion. The patient recovered fairly but was readmitted 3 months later with a massive left hemispheric hemorrhage seen on the computed tomography scan displayed in the lower row. Notice again the heterogeneous characteristic of the lesion in this very early phase.

Figure 11-3 Brain magnetic resonance imaging shows extensive leukoaraiosis on fluid-attenuated inversion recovery sequence (upper left) associated with multiple cortical microhemorrhages in the cerebellar (upper right) and cerebral hemispheres (lower row) best seen on gradient-recall echo/T2* sequence.

HEMORRHAGIC TRANSFORMATION

Hemorrhagic transformation is common during the evolution of large ischemic strokes, particularly those caused by embolism. In the majority of cases, the hemorrhagic component is seen on computed tomography (CT) or MRI scan but does not produce clinical deterioration. However, some patients develop a true hematoma within the infraction, and the resulting mass effect may be rapidly fatal. These cases of “malignant” hemorrhagic transformation are most often associated with the use of anticoagulation or thrombolysis. Brain imaging may provide helpful clues to avoid this devastating complication. Hemorrhagic complications after thrombolysis represent a particularly important form of hemorrhage after ischemic infarction and are discussed separately in the next section.

Case Vignette

An 86-year-old woman with history of hypertension and right parietal meningioma was found unresponsive on her bed during a cruise. She was intubated and emergently transferred to our hospital for evaluation. On arrival, she was drowsy, globally aphasic, and had flaccid right hemiplegia. Her pulse was irregularly irregular, and electrocardiogram confirmed the diagnosis of atrial fibrillation. Initial CT scan is shown in Figure 11-4, A and B.

Figure 11-4 (A) Large left middle cerebral artery infarction seen on the computed tomography scan of the head with contrast (upper row). Notice blockage of flow in the middistal M1 segment (arrow) and early contrast extravasation in the core of the infarction., Signs of hemorrhagic conversion of the ischemic infarction are seen on computed tomography scan (C). T1-weighted magnetic resonance imaging with gadolinium demonstrates linear areas of contrast enhancement within the infarction (D). Fluid-attenuated inversion recovery sequence shows heterogeneous signal change in the area of ischemia complicated with hemorrhagic transformation (E). Gradient-recalled echo sequence clearly discloses the hemorrhagic changes of the infarction (F).

Case Vignette

CT scan of the head and brain MRI obtained 48 hours after symptom onset showed evidence of hemorrhagic transformation (Figure 11-4, C–F). The patient had been taking aspirin before the stroke, and 325 mg of aspirin had been administered since admission. Anticoagulation had not been initiated because of the perceived high risk of hemorrhagic conversion of the ischemic infarction. On the third day after stroke onset, the patient’s neurological status deteriorated because of progression of mass effect. She responded favorably to treatment with mannitol. Her subsequent clinical course was complicated with the development of acute renal failure, congestive heart failure, bilateral pneumonia, and sepsis. She required tracheostomy and was eventually transferred to a nursing home in fair condition. Six months later, she had improved communication abilities but remained functionally dependent.

♦ MRI is more sensitive than CT scan for the diagnosis and quantification of hemorrhagic transformation of ischemic infarction.

♦ Hemorrhagic transformation is most often asymptomatic. It tends to affect focal areas of the infarction, frequently close to the cortex (where blood probably arrives from leptomeningeal collaterals) (Figures 11-5, 11-6, and 11-7).

♦ Hemorrhagic transformation is often associated with early contrast parenchymal enhancement, also a marker of disrupted blood-brain barrier.¹⁵

♦ MRI is particularly superior to CT scan for the detection of hemorrhage after intra-arterial thrombolysis, when extravasated contrast may be confused with blood.¹⁶

♦ Hemorrhage may be facilitated by delayed recanalization of the occluded vessel due to clot autolysis (or therapeutic thrombolysis) (Figure 11-8).

♦ Radiological evidence of asymptomatic hemorrhagic transformation should be carefully considered when deciding the timing of initiation of anticoagulation in patients with large embolic strokes.

♦ Even pronounced hemorrhagic conversion of a small infarction may be safe, whereas lesser degrees of hemorrhage into large infarctions may precipitate herniation.

♦ In our experience, the risk of symptomatic severe hemorrhagic transformation is greater in patients with proximal middle cerebral artery (MCA) occlusions in whom the infarction involves the territory perfused by the lenticulostriate branches (Figure 11-9).

♦ Hemorrhage into the deep ganglia often results in rapid and often fatal herniation (Figure 11-9).

Figure 11-5 Multiples examples of hemorrhagic conversion of ischemic infarctions on head computed tomography scans.

Figure 11-6 Brain imaging displaying a cortical area of hemorrhagic conversion of a large anterior cerebral artery infarction. A, Computed tomography scan of the head with hemorrhagic region signaled by arrow. B, Diffusion weighted imaging with acute infarction exhibiting restricted diffusion (bright signal) and hemorrhage distinguished by increased diffusion (dark signal). C, T1-weighted sequence displays the hemorrhage with isointense signal, indicating acute bleeding. D, fluid-attenuated inversion recovery sequence with increased signal in the area of ischemic infarction and decreased signal in the zone of hemorrhagic conversion.

Figure 11-7 A 62-year-old man who suffered a large left middle cerebral artery embolic infarction from cardiac embolism caused by atrial fibrillation. Diffusion-weighted imaging and apparent diffusion coefficient map are shown in the upper row, T1-weighted sequence before and after gadolinium administration in the middle row, fluid-attenuated inversion recovery in the left frame of the lower row and gradient-recalled echo (GRE) in the right frame of the lower row. Note contrast extravasation in the contrast-enhanced T1-weighted image and small areas of hemorrhagic conversion on GRE.

Figure 11-8 A 58-year-old man with acute left middle cerebral artery occlusion due to atrial fibrillation was evaluated in the emergency department of the referring hospital 5 hours after symptom onset. Head computed tomography (CT) scan at that time (left) showed an extensive hyperdense middle cerebral artery sign (arrow). By the time he arrived to our hospital, he was beyond the window for intra-arterial therapy. On the second day of admission, he was found unresponsive in the stroke unit. Emergency CT scan (right) showed resolution of the hyperdensity in the middle cerebral artery (clot autolysis) and revealed extensive hemorrhage in the area of the deep nuclei with intraventricular extension and marked regional mass effect.

Figure 11-9 Two examples of “malignant” hemorrhagic transformation involving the deep portions of middle cerebral artery infarctions and causing severe tissue displacement. The complication was fatal in both cases. Computed tomography (CT) scans of first case shown in upper row. Second case is illustrated by CT scan (left) and fluid-attenuated inversion recovery sequence of magnetic resonance imaging (right) in the lower row.

HEMORRHAGIC COMPLICATIONS OF THROMBOLYSIS

Intracranial hemorrhage is the most feared complication of thrombolysis. Symptomatic hemorrhagic transformation occurs in 6% to 7% of patients who receive treatment with recombinant tissue plasminogen activator (rt-PA) within 3 hours of symptom onset.^17,¹⁸ The rate of hemorrhage is about 10% after intra-arterial lysis.¹⁹ Hemorrhagic risks with combined intravenous–intra-arterial lysis²⁰ and mechanical embolectomy²¹ also fall within this range. It tends to occur early after infusion of rt-PA and carries high mortality. However, it does not negate the value of thrombolysis in appropriate candidates for this acute intervention.

Clinical factors include older age, pretreatment hypertension, pretreatment hyperglycemia, history of diabetes mellitus, use of antiplatelets other than aspirin before stroke onset, greater stroke severity (i.e., higher score on the National Institutes of Health stroke scale) at baseline, and higher blood pressure over the first 24 hours after lysis.²²^–²⁶ Radiological predictors on initial CT scan include hypodense lesion greater than one third of MCA territory and hyperdense MCA sign.^22,²³ MRI with diffusion-weighted imaging/perfusion-weighted imaging (DWI/PWI) may be particularly useful because very low initial apparent diffusion coefficient (ADC) values, persistent perfusion deficits on PWI, and very large areas of restricted diffusion on DWI strongly correlate with heightened risk of hemorrhagic transformation.^22,²⁷^–³¹ Although DWI and PWI are not usually available when thrombolysis is administered within the 3-hour window, the predictive information provided by these sequences may become important if thrombolysis is considered at later times in patients with persistent radiological penumbra. Leukoaraiosis has also been associated with increased risk of ICH after thrombolysis.³² However, the presence of cerebral microhemorrhages seen on T2* sequence does not appear to influence substantially the risk of symptomatic ICH.³³ Although the factors influencing the risk of hemorrhage after intra-arterial thrombolysis or multimodality therapy have been less studied, available evidence indicates that they do not differ significantly from those that determine the risk after intravenous lysis.^34,³⁵

It has been appropriately postulated that the deleterious consequences of symptomatic ICH after thrombolysis may have been overestimated by failing to consider the predicted outcome at the time of initial assessment in patients who subsequently had symptomatic ICH.³⁶ Because outcome in many of these patients is anticipated to be poor (because of older age, more severe deficits, and larger strokes), when the predicted functional outcome is compared with the actual outcome after ICH, the number necessary to harm for intravenous thrombolysis turns out to be much smaller than commonly thought. In other words, symptomatic ICH after thrombolysis may further worsen outcome in patients with poor chances of recovery without thrombolysis, but it rarely causes devastating damage in patients with better anticipated outcome at the time of treatment.

Case Vignette

A 68-year-old man with previous history of a left hemispheric stroke presented to the emergency department with sudden onset of left-sided weakness within 2 hours of symptom onset. Examination revealed right gaze preference, left homonymous hemianopia, left hemiparesis, and partial left hemibody neglect. Initial CT scan is shown in Figure 11-10 (upper row). He had no contraindications for intravenous thrombolysis and consequently received rt-PA with the bolus given 2 hours and 45 minutes after instauration of deficits. Three hours later, the patient was noticed to be somnolent, and his weakness had worsened to the point of hemiplegia. Emergent repeat CT scan displayed intraparenchymal and subarachnoid hemorrhage (Figure 11-10, middle row). He was treated with fresh frozen plasma and cryoprecipitate. Although his deficits remained severe, he subsequently improved. Brain MRI on day 5 showed the hemorrhagic transformation of his right MCA infarction with mild regional mass effect (Figure 11-10, lower row).

Figure 11-10 Initial computed tomography (CT) scan of the head (upper row) shows possible subtle changes of right middle cerebral artery territory ischemia, old areas of left frontal and insular infarction, and areas of periventricular white matter rarefaction. Emergency CT scan at the time of clinical decline (middle row) reveals hemorrhage in the area of the acute right hemispheric infarction (arrows) and extensive subarachnoid bleeding. Brain magnetic resonance imaging (lower row; fluid-attenuated inversion recovery on the left and gradient-recall echo on the right) allows more detailed identification of the acute infarction with hemorrhagic conversion, subarachnoid hemorrhage, and areas of old ischemia.

♦ Symptomatic ICH after thrombolysis typically occurs within the first few hours after treatment.

♦ Clinical manifestations are characteristically severe, often compromising alertness. Fatal outcome is not uncommon (Figure 11-11).

♦ Most hemorrhages occur in the area of the infarction, and they are related to the severity and duration of the ischemia.³⁷ Distant parenchymal hematomas occur uncommonly, and they may be asymptomatic or devastating.

♦ After ICH is confirmed by means of emergency CT scan, treatment with fresh frozen plasma, cryoprecipitate, and perhaps platelet transfusion is indicated. The efficacy of these treatments is uncertain. Neurosurgical consultation is recommended, but in our experience, the resulting hematomas are almost never evacuated acutely because of the understandable concern about inadequate hemostasis.

Figure 11-11 Additional example of massive and fatal intracranial hemorrhage after intravenous thrombolysis for acute left hemispheric stroke.

ANTICOAGULATION-RELATED INTRACEREBRAL HEMORRHAGE

The incidence of ICH associated with anticoagulation is growing with the aging of the general population. It is said that these hemorrhages have a greater propensity to enlarge, with hematoma growth occurring earlier and for longer time than in primary ICH. It is also assumed that the prognosis may be markedly improved if anticoagulation is promptly reversed. Both perceptions are based on uncontrolled case series and anecdotal experience and remain to be proved in rigorous studies. Nonetheless, the necessity to recognize anticoagulation as the source of the bleeding and reverse it as soon as safely possible is undeniable. Certain radiological features apparent on the initial CT scan are characteristic, although not pathognomonic, of hemorrhages related to anticoagulation or endogenous abnormal coagulation. These features are illustrated in the following case.

Case Vignette

A 62-year-old man with history of atrial fibrillation, myocardial infarction, diabetes mellitus, and hypertension developed sudden dysarthria and right hemiparesis with hemisensory loss. International normalized ratio on admission was 4.2. Head CT scan is shown in Figure 11-12 (upper row). Anticoagulation was reversed with fresh frozen plasma and vitamin K. The following day, the patient was more somnolent, anarthric, and hemiplegic. Repeat CT scan revealed enlargement of the hematoma without signs of herniation. Over the next 12 hours, he became stuporous, and a third CT scan showed a 9-mm shift of the septum pellucidum (Figure 11-12, lower row). He underwent surgical evacuation of the hematoma and progressively improved after surgery. He initially required tracheostomy and percutaneous gastrostomy, but 3 months later, his tracheostomy was closed, he was eating without major difficulties, was able to communicate, and had only moderate disability from his right hemiparesis.

Figure 11-12 Initial head computed tomography (CT) scan showing a deep intracerebral hematoma in the left hemisphere (upper row). Notice fluid level on the left frame, a sign highly suggestive of underlying coagulation abnormality. Lower row displays follow-up CT scan demonstrating massive expansion of the hemorrhage causing severe shift of the midline structures.

♦ The clinical presentation is often characterized by progression of neurological deficits over several hours (up to 24–48 hours),³⁸ probably reflecting the gradual accumulation of blood in the growing hematoma.

♦ In fact, warfarin use may be associated with greater risk of expansion without necessarily influencing the initial hematoma volume.³⁹

♦ Hematomas tend to be large and are associated with high mortality rates (40%–60%).³⁸^–⁴³ Unconsciousness on admission, hematoma size greater than 60 cc, and intraventricular extension of the hemorrhage are reliable predictors of fatal outcome.³⁸

♦ Lobar and cerebellar locations predominate, but the epicenter of the bleeding may be in the basal ganglia or their proximities.⁴⁰

♦ Fluid levels are the most typical feature of anticoagulation-related ICH (although they may also be seen in patients with other coagulation disorders and in cases provoked by thrombolysis or combination of antiplatelet agents).

♦ Hematomas frequently exhibit heterogeneous appearance, with areas of different density on CT scan. This heterogeneity is better appreciated on MRI, a technique that also allows assessment of the age of the constituent parts of the hematoma.

♦ It may be reasonable to obtain serial CT scans at regular intervals in patients with anticoagulation-related ICH over the first 48 hours because of the high likelihood of hematoma growth.

♦ Anticoagulation should be promptly reversed; however, we have observed cases of fatal hematoma expansion even hours after full reversal of anticoagulation.⁴⁴

♦ Timely surgical evacuation of anticoagulation-associated hematomas with marked mass effect may allow favorable functional recovery,⁴⁵ as illustrated by our case.

♦ Several additional examples of anticoagulation-associated ICH are shown in Figure 11-13.

Figure 11-13 Three additional examples of intracerebral hemorrhage associated with anticoagulation. Upper row: Extensive acute left frontal hemorrhage on computed tomography scan. Middle row: Large acute to early subacute right frontoparietal hemorrhage on brain magnetic resonance imaging (T1-weighted imaging on the left and T2-weighted imaging on the right). Lower row: Fatal right frontal hematoma with massive subfalcine herniation. Notice the characteristic heterogeneity of the signal changes and fluid levels in the cases depicted.

COAGULOPATHY

Case Vignette

A 60-year-old man was found unresponsive by his wife and brought emergently to the emergency department. On arrival, he was stuporous, had a right fixed dilatated pupil, and exhibited no response to pain on the left limbs and withdrawal responses on the right. He had multiple purpuric lesions throughout his body and history of “easy bruising and poor clotting” according to his wife. Splinter hemorrhages were noted in his nail beds. Initial CT scan is shown in Figure 11-14. Platelet count was 8000 per mm³, and peripheral smear disclosed multiple atypical immature circulating lymphoid cells. He continued to deteriorate rapidly despite multiple platelet transfusions and was declared brain dead 18 hours later. Necropsy revealed evidence of acute myelocytic leukemia.

Figure 11-14 Upper row: computed tomography scan shows a large intracerebral hemorrhage extending through the right frontal, temporal, and parietal lobes. Note the irregular borders and heterogeneous density of the hematoma. Lower row: magnetic resonance imaging confirms the acute nature of the hematoma indicated by the isointense signal on T1-weighted sequence (left) and dark signal on T2* sequence (right). Arrow point to the evidence of uncal herniation.

♦ ICH due to intrinsic coagulation disorders may occur spontaneously or following apparently innocent trauma (especially in patients with hemophilia ⁴⁶).

♦ Location is most often lobar, but deep hematomas may occur.

♦ Multiple hematomas of different volume and age may coexist (e.g., in the case of leukemias).⁴⁷

♦ Subdural hematomas may be present, particularly when the bleeding is posttraumatic.⁴⁶

♦ The imaging characteristics are similar to those seen in cases induced by anticoagulation (i.e., large heterogeneous hematomas, often with fluid levels and poorly demarcated boundaries).

♦ Expansion is common and may occur later than in cases of spontaneous ICH (Figure 11-15).

♦ Mortality is elevated, and the most common causes are brain herniation and concurrent systemic bleeding.

Figure 11-15 Additional example of intracerebral hemorrhage induced by a coagulopathy with evidence of early expansion. This 45-year-old woman had history of severe idiopathic thrombocytopenia and presented with acute aphasia and left hemiparesis. Initial computed tomography (CT) scan is shown in the upper row. Note fluid level and different densities within the core of the hematoma. Despite platelet transfusions, she worsened over the following hours and became comatose. Repeat CT scan (lower row) confirmed that the hematoma had enlarged considerably, consequently producing severe subfalcine herniation. The patient expired 2 days later.

SUBSTANCE ABUSE

♦ Use of cocaine and amphetamines is a common cause of ICH in young patients. Isolated cases have also been reported with “ecstasy” and phencyclidine (PCP).

♦ Although underlying vascular malformations have been reported in some cases of ICH associated with illicit drug use,^48,⁴⁹ the sympathomimetic effects of these recreational drugs are most likely responsible for the majority of the events.

♦ The concept that acute hypertension is the responsible pathophysiological mechanism is supported by the preponderance of ganglionic hematomas in our cases (Figures 11-16 and 11-17). However, previous literature indicates that lobar locations are common.⁵⁰

♦ Subarachnoid and intraventricular hemorrhages may accompany the intraparenchymal hematoma or may occur in isolation.

♦ In our opinion, angiography should be performed in patients with lobar hematomas, subarachnoid hemorrhage, or predominant intraventricular bleeding. However, we have found angiography to have minimal yield in patients with classical ganglionic pattern and positive toxicological screen for cocaine or amphetamine.

♦ It is important to remember that decongestants and appetite suppressants (such as phenylpropanolamine and pseudoephedrine) also produce hematomas caused by acute hypertension. The locations of these hemorrhages are those typically observed in spontaneous (hypertensive) cases.

Figure 11-16 This 38-year-old man with long-standing history of cocaine use was found unresponsive in the street and brought to our emergency department. On arrival, his blood pressure was 210/118. His computed tomography scan showed a massive right ganglionic hematoma with pronounced midline shift. He was declared brain dead 36 hours later.

Figure 11-17 This figure shows three additional examples of intracerebral hemorrhages precipitated by substance abuse (cocaine in all cases; one of the patients had also used ectasy). Notice predominant deep, ganglionic locations. The patient presented in the lower row had concurrent hemorrhages in the right thalamus and left parieto-occipital region; cerebral angiography did not identify underlying vascular anomalies or vasculitis.

INFECTIVE ENDOCARDITIS

Case Vignette

A 51-year-old man presented with complaints of fever with chills, myalgias, arthralgias, diarrhea, and profound malaise for 1 week. He used intravenous cocaine but had no documented previous illnesses. On examination, the patient appeared acutely ill and was febrile. Cardiac auscultation revealed galloped tachycardia and a diastolic cardiac murmur. Hepatosplenomegaly was apparent on abdominal auscultation. Admission blood tests showed pronounced leukocytosis, and the patient was started empirically on antibiotics after blood cultures had been obtained. In less than 24 hours, oxacillin-sensitive Staphylococcus aureus was isolated from the blood cultures. Transthoracic echocardiography demonstrated an aortic valve vegetation (Figure 11-18) with evidence of valvular regurgitation. Complaints of headaches and visual changes prompted a neurological consultation. Left homonymous visual field deficit was evident on examination. Roth spots were seen on fundoscopy. Brain imaging disclosed multiple hemorrhagic and ischemic lesions diffusely distributed in both cerebral hemispheres and the left cerebellum (Figure 11-18). Abdominal CT scan also showed embolic lesions in the liver, spleen, and both adrenal glands. The patient refused surgery but responded well to intravenous antibiotics, with no further clinical evidence of systemic embolism.

Figure 11-18 Transthoracic echocardiogram (upper row, left) demonstrating a vegetation attached to the aortic valve (arrow). Brain imaging disclosed a combination of hemorrhagic and ischemic lesions, including a right occipital hematoma (seen on computed tomography [CT] scan in the middle frame of the upper row, on T1-weighted sequence in the middle frame of the second row, and on gradient-recall echo on the right frame of the second row), a left posterior frontal ischemic infarction (visualized as a low attenuation region on CT scan marked by the arrowhead in the right frame of the upper row and as a bright area of restricted diffusion on diffusion-weighted imaging (DWI) in the right frame of the second row), and a small hemorrhagic infarction in the left cerebellar hemisphere (indicated by the solid arrow in the magnified CT scan shown in the left frame of the bottom row; DWI disclosed that the lesion had restricted diffusion as presented in the right frame of the same row).

♦ Infective endocarditis may cause ICH when a septic (mycotic) aneurysm ruptures.

♦ Infective endocarditis may also be associated with subarachnoid or intraventricular hemorrhage. Subarachnoid hemorrhage typically overlies the hemispheric convexity and may spare the basal cisterns.

♦ Conventional angiography is necessary to identify the underlying aneurysm, given that their small size may be below the detection threshold of noninvasive angiographic techniques.

VASCULITIS

♦ The combination of acute small ischemic and hemorrhagic lesions should raise the suspicion of underlying vasculitis.

♦ However, territorial infarctions and larger hematomas may occur. In fact, fatal hemorrhages caused by infectious or autoimmune necrotizing vasculitis have been reported.⁵¹

♦ Hemorrhagic foci may be multiple and widespread ⁵² (Figure 11-19). Cerebral hemispheres, cerebellum, and brainstem may be involved.

♦ The value of angiography for the diagnosis of vasculitis is a matter of unresolved debate. Characteristic irregularities (“string of beads”) of cerebral vessels in patients with known systemic vasculitis may suffice to support the diagnosis and justify immunosuppression (Figure 11-19). It may also be acceptable to base the diagnosis on appropriate clinical manifestations and typical angiographic changes in certain cases of primary central nervous system vasculitis.⁵³

♦ Definitive diagnosis can only be made by pathological examination of a biopsy sample. In cases with clinical suspicion of vasculitis, angiographic findings have been found to correlate poorly with MRI appearance and biopsy results.^54,⁵⁵ However, biopsies may be negative in patients with angiographic changes of central nervous system vasculitis because vessel involvement is not uniformly distributed throughout the circulation.⁵³

Figure 11-19 A 52-year-old woman presented with subacute headache and progressive confusion and acute left-hand weakness. Computed tomography scan (upper row) revealed foci of hemorrhage in the left lenticular nucleus and cortex of the higher portion of the right frontal lobe (arrowheads). Catheter cerebral angiography (lower row) revealed multifocal vascular irregularities (“beading”) suspicious for vasculitis (arrows). The patient had no symptoms or signs of systemic vasculitis. Brain biopsy targeted to the right frontal lesion confirmed the diagnosis of primary central nervous system vasculitis. The patient improved after treatment with immunosuppression.

CEREBRAL VENOUS THROMBOSIS

Case Vignette

A 38-year-old woman without significant past medical history was brought to the emergency department with new onset tonic-clonic seizures. She had been complaining of increasing headaches for the previous week. On examination, the patient was confused and had right hemiparesis. Coagulation values were normal. Head CT revealed bifrontal hemorrhages with abundant edema and small right frontal subarachnoid hemorrhage as shown in Figure 11-20. Subsequent brain MRI better delineated the extent of the multiple hemorrhagic lesions, and MR venography (MRV) confirmed the suspected diagnosis of cerebral venous sinus thrombosis. She was treated with intravenous heparin and antiepileptics. Despite extensive evaluation, no evidence of an underlying hypercoagulable disorder was found. However, the patient had started to take oral contraceptive pills a few weeks before the onset of her neurological symptoms. She recovered well and was discharged to the rehabilitation unit. Four months later, she had experienced no recurrent seizures, was free of headaches, and had only minimal functional impairment.

Figure 11-20 Upper row: computed tomography scan showing areas of acute hemorrhagic infarction in the right frontal and high left frontal lobes. A third area of low attenuation in the high right frontal lobe is also suspicious for infarction. Second row: fluid-attenuated inversion recovery sequence (left) confirms the presence of three frontal lesions, two with hemorrhagic component. Gradient-recall echo demonstrates additional areas of hemorrhage and also shows that the hemorrhages have different ages: small anterior right frontal lesion is early subacute (bright lesion pointed by the solid arrow), and multiple other lesions are more acute (dark lesions indicated by the thinner arrows). Third row: Coronal (left) and axial (right) T1-weighted sequence showing another lesion in the left cerebellar hemisphere just below the tentorium. Fourth row: Sagittal T1-weighted sequence (left) showing abnormal flow signal in the area corresponding to the posterior third of the superior sagittal sinus (arrowhead). Magnetic resonance venography confirmed the diagnosis of dural sinus thrombosis by revealing occlusion of the left transverse and sigmoid sinuses and an area of absent flow in the posterior superior sagittal sinus.

♦ Hemorrhagic venous infarctions are the mechanism of production of cerebral and cerebellar hematomas in patients with cerebral venous thrombosis.

♦ Hemorrhages typically develop in close proximity to the major venous sinuses (e.g., parasagittal hematomas in cases of superior sagittal sinus thrombosis, superficial posterior temporal hematomas in patients with transverse sinus thrombosis). However, hemorrhages may also occur after occlusion of smaller venous structures, such as superficial branches draining into the major sinuses (e.g., frontal lesions in the case vignette) or deep cortical veins (e.g., bilateral thalamic hemorrhages).

♦ Multiple hemorrhagic infarctions may coexist in patients with extensive venous thrombosis, as illustrated in our case vignette.

♦ MRI combined with MRV has excellent sensitivity for the diagnosis of venous sinus thrombosis.^56,⁵⁷ The diagnosis of cortical vein thrombosis is most often difficult to prove even with conventional angiography.

♦ Anticoagulation is safe even in patients with large hematomas.⁵⁸ Despite lack of definitive proof of statistically significant benefit from randomized controlled trials, most available data favor the use of anticoagulation.⁵⁹ In fact, anticoagulation is applied in most cases of cerebral venous thrombosis.⁶⁰ Late initiation of anticoagulation may be associated with worse outcome.⁶¹

♦ Mechanical thrombolysis may be valuable in patients with rapidly progressive neurological decline and massive sinus thrombosis.⁶² Endovascular local thrombolysis appears to be safe and may also be an effective alternative.⁶³

♦ Decompressive craniectomy is a reasonable option in patients with signs of impending or established herniation. This intervention is compatible with favorable recovery in young patients with cerebral venous thrombosis.⁶⁴

♦ We present a more detailed discussion of this topic in Chapter 14.

ARTERIOVENOUS MALFORMATIONS

♦ Symptomatic hemorrhage is the form of presentation of arteriovenous malformations in 60% of patients.⁶⁵

♦ Arteriovenous malformations typically produce single hemorrhages, with predominant lobar location (although they may occur in the depth of the brain, posterior fossa, or spinal cord) and variable volume (Figures 11-21 and 11-22).

♦ Subarachnoid hemorrhage may accompany the intraparenchymal hematoma and may constitute the predominant finding in some patients.

♦ Vascular calcifications may be identified on CT scan. Their presence should be considered highly suspicious for arteriovenous malformation.

♦ MRI is considerably more sensitive than CT scan for the recognition of the vascular malformations. Arteriovenous malformations display a characteristic appearance resembling a honeycomb of serpiginous flow voids (Figures 11-21 and 11-22).

♦ Noninvasive angiographic modalities may confirm the presence of the malformation, except when the lesion is very small or thrombosed.

♦ Selective catheter angiography is always necessary to define the angioarchitecture of the lesion (arterial feeders, aneurysm in the nidus or the pedicle, draining veins).

♦ T2* gradient recall echo has excellent sensitivity for the diagnosis of older hemorrhagic foci (hypointensity with “blooming” effect generated by the presence of hemosiderin).

♦ After an episode of symptomatic hemorrhage, the risk of new hemorrhagic events increases, but the magnitude of this effect is not well established. Annual rates of rehemorrhage have ranged from 2% (6% during the first year)⁶⁶ to 18%⁶⁷ in various observational studies.

♦ Arteriovenous malformations are discussed in greater detail in Chapter 13.

Figure 11-21 Upper row: computed tomography scan shows an area of acute hemorrhage in the left insular region (left, arrowhead) associated with a serpiginous high attenuation highly suggestive of an arteriovenous malformation (right, open arrow). Second row: Brain magnetic resonance imaging (T1-weighted sequence on the left and fluid-attenuated inversion recovery on the right) display characteristic changes compatible with arteriovenous malformation: fluid voids and honeycomb appearance. Third row: Enhanced T1-weighted sequence (axial on the left and coronal on the right) allows further discrimination of the vascular lesion. Solid arrow indicates large draining vein.

Figure 11-22 Vermian hemorrhage on computed tomography scan (left) caused by a left cerebellar arteriovenous malformations, which is well seen on fluid-attenuated inversion recovery magnetic resonance imaging (right).

CAVERNOUS MALFORMATION

♦ Cavernous malformations usually produce relatively small, contained hemorrhages (Figure 11-23).

♦ The vascular anomaly can only be diagnosed using MRI, particularly the T2*-gradient-recall echo sequence. Because these lesions are not connected to the arterial or venous circulations, they are not visualized on angiography.

♦ Multiple, widespread lesions are common (Figure 11-23). When a single cavernous malformation presents with hemorrhage, the diagnosis may only be possible by repeating the brain MRI a few weeks after the bleeding episode.

♦ The annual rebleeding rate may range between 3% and 4.5%.^68,⁶⁹

♦ Hemorrhages caused by cavernous malformations tend to have benign prognosis, but recurrent hemorrhages in eloquent brain locations may constitute a formidable problem.

Figure 11-23 Multiples cavernous angiomas in a 38-year-old woman presenting with a brainstem syndrome. Upper row: Acute to early subacute hemorrhage in the right pontine tegmentum is shown by T1-weighted and gradient-recall echo (GRE) sequences (thin arrows). Lower row: Additional foci of hemorrhage are present in both cerebral hemispheres as displayed by the T2-weighted image on the left, which shows a right parietal lesion with the characteristic “popcorn-ball appearance” (solid arrow), and the GRE sequence of the right showing small foci of hemorrhage in the left frontal and right periatrial regions (arrowheads).

DURAL ARTERIOVENOUS FISTULA

♦ Hematomas are usually located near the base of the skull (Figure 11-24) and always adjacent to the affected dural sinus (transverse sinus is the most commonly involved).

♦ Brain MRI may suggest the diagnosis (thrombosed sinus isointense on T2-weighted and fluid-attenuated inversion recovery sequences and flow voids from engorged pial veins), especially when MRV is also performed. Conventional angiography is necessary to characterize the fistula and evaluate the pattern of drainage.

♦ Presence of retrograde leptomeningeal venous drainage is associated with aggressive clinical course. Risk of hemorrhage is maximal in patients with direct cortical drainage and venous ectasia.⁷⁰

♦ Refer to Chapter 13 for a detailed discussion of dural fistulas.

Figure 11-24 Midline cerebellar hematoma seen on computed tomography scan (left) and sagittal T1-weighted magnetic resonance imaging with gadolinium (right) caused by angiographically proven dural arteriovenous fistula.

TUMOR

♦ Tumors may be first diagnosed when bleeding in their core leads to enlargement of their volume and exertion of mass effect.

♦ The primary tumors with greatest propensity to become hemorrhagic are glioblastoma multiforme (Figure 11-25) and lymphoma. Less common primary tumors such as hemangioblastoma and hemangiopericytoma should also be considered. Hemorrhagic brain metastases are most common with melanomas (Figure 11-26), lung carcinoma, hepatocellular carcinoma, and renal cell carcinoma.

♦ The most characteristic radiological sign of hemorrhagic tumors is their extensive vasogenic edema, which is out of proportion to what would be expected for the size of the hemorrhagic mass.

♦ Contrast MRI is often diagnostic. However, delayed imaging may be necessary when the hemorrhage is large and obscures the underlying mass.

♦ A hemorrhagic component of a tumoral mass may be reliably diagnosed using T2*-gradient recall echo sequence.

♦ Presence of a midline hemorrhagic mass in a patient with depressed level of consciousness should be treated as pituitary apoplexy until proved otherwise.