70 Intraventricular Hemorrhage

J. MAX FINDLAY

B leeding directly into the ventricles from a source or

lesion that is in contact with or is part of a ventricular
wall, such as a vascular malformation or neoplasm, is clas-
choroid plexus papilloma,17 intraventricular meningi-
oma,18,19 pituitary tumors that erode through the floor
of the third ventricle,20 neurocytoma,21 granular cell
sified as primary intraventricular hemorrhage (IVH). This tumor,22 metastasis,23 and craniopharyngioma (Fig. 70-1).
type of IVH without an associated intracerebral hematoma It is probable that any cause of spontaneous ICH can be
is rare, accounting for only about 3% of all spontaneous responsible for direct bleeding into the ventricles.
intracerebral hemorrhages (ICHs).1 Much more commonly,
IVH is secondary either to intracerebral bleeding that dis- Hypertensive Brain Hemorrhage
sects through brain parenchyma to reach a ventricle or
and Intraventricular Hemorrhage
to bleeding into the subarachnoid space that spreads into
the ventricles through the fourth ventricular foramina. Pri- Spontaneous hypertensive ICHs are associated with sec-
mary or secondary IVHs can fill one or more ventricles and, ondary IVH in one third to one half of patients.24 The most
when of sufficient volume and density, can result in formed significant risk factor for this arteriopathy, which most
ventricular blood clots, or hematocephalus. Blood that commonly affects the lenticulostriate and thalamoperfo-
refluxes into the ventricles from the subarachnoid space rating arterioles, is chronic arterial hypertension; other risk
often remains unclotted and settles in dependent parts of factors are moderate to heavy alcohol intake and antico-
the ventricular system.  Although the presence of IVH per agulant treatment.25 IVH most often complicates thalamic,
se does not always correlate with neurologic condition or caudate, or putaminal bleeding that decompresses into
prognosis, IVH is an independent and important clinical the lateral or third ventricles (Fig. 70-2). Not surprisingly,
problem when clots distend the ventricular system, com- IVH in this setting has been associated with larger paren-
press adjacent brain, or obstruct cerebrospinal fluid (CSF) chymal hematomas, midline shift of brain structures, and
flow to cause hydrocephalus and elevated intracranial pres- worse clinical outcome.26-28 Patients with spontaneous
sure (ICP). and deep intracerebral hemorrhages complicated by both
There are many causes of spontaneous IVH, but the IVH and hydrocephalus have a particularly bad progno-
most common are hypertensive ICH, saccular aneurysms, sis,29-31 although the associated ICH size probably has the
and arteriovenous malformations (AVMs).2-8 IVH resulting greatest influence on clinical outcome.32
from germinal matrix hemorrhage in the newborn and
traumatic IVH are not discussed in this chapter. Aneurysmal Intraventricular Hemorrhage
Of patients who survive rupture of an intracranial aneu-
Primary Intraventricular Hemorrhage
rysm, IVH is seen in roughly 15% of the entire group, in 25%
Spontaneous IVH with no evidence of associated ICH is of those with severe subarachnoid hemorrhage (SAH), and
most often due either to a vascular malformation that con- in 40% of those who subsequently die from the rupture.33
tacts the ependyma of one of the ventricular chambers or Aneurysmal IVH is associated with an up to 50% chance
to an intraventricular or periventricular neoplasm.7 There of requiring a ventriculoperitoneal shunt.34-36 Aneurysm
have been rare reports of primary IVH due to ruptured rupture can cause IVH through several different mecha-
intraventricular aneurysms, which arise from distal lenticu- nisms.37 Blood can reflux into the ventricular system
lostriate or choroidal arteries that reach the ventricular lin- from an aneurysm in any location, but disproportionate
ing or choroid plexus.9 Aneurysms have been reported on or isolated fourth ventricular hemorrhage in association
penetrating arteries enlarged by moyamoya disease.10-12 In with SAH is especially suggestive of a posterior circulation
some cases, no cause of primary IVH can be established, aneurysm situated closer to the fourth ventricular foram-
although in these instances bleeding may be from rup- ina. Up to one half of posterior inferior cerebellar artery
ture of arterioles located in the immediate periventricular (PICA) aneurysm ruptures have an accompanying IVH.38
region that have been weakened by chronic hypertension. Sudden death from aneurysmal SAH is commonly asso-
Primary IVH can be due to any type of bleeding disorder, ciated with IVH, and in some patients the mechanism
including anticoagulation8 and fibrinolytic treatment.13,14 may be acute fourth ventricular dilatation causing brain-
The most common brain neoplasm that bleeds sponta- stem compression.39,40
neously is malignant astrocytoma. Less common tumors to Aneurysms also cause IVH when forceful hemorrhage
cause primary IVH are ependymoma,15 subependymoma,16 dissects through intervening brain parenchyma to reach
1349
1350 THERAPY

the ventricular system.This occurrence is most commonly Vascular Malformations and

seen with anterior communicating artery aneurysms.41
Intraventricular Hemorrhage
With a 25% incidence of associated IVH, this aneurysm
is the most common type to cause IVH. Blood can break Cerebral AVMs that are in contact with the ventricular
directly through the lamina terminalis into the third ven- wall and hemorrhage often bleed into the ventricles,
tricle or can pass superiorly beneath the rostrum of the and are usually associated with deep cerebral venous
corpus callosum to leak through the septum pellucidum drainage (Fig. 70-4). In one prospective AVM database,
into the lateral ventricles. Frontal hemorrhages resulting 16% of first AVM hemorrhages were primarily intra-
from anterior communicating or middle cerebral artery ventricular and 31% were combined intracerebral and
aneurysms can spread into the anterior horn of the lateral intraventricular hemorrhages.44 Periventricular cavern-
ventricles. ous malformations and dural arteriovenous fistulas with
Internal carotid artery aneurysms, at the origin of either transcerebral venous drainage are less common but can
the posterior communicating or the anterior choroidal also cause IVH.
arteries can rupture into the temporal horn of the lateral
ventricles (Fig. 70-3). Basilar apex aneurysms can rupture Natural Clearance of Intraventricular
directly through the hypothalamus to reach the third ven-
Hemorrhage
tricle, usually with serious clinical consequences.
In large patient series, IVH along with aneurysm rup- Normally the CSF contains little fibrinolytic activity,
ture is associated with higher intracranial pressures42 and although fibrinolysis becomes detectable after bleed-
worse outcome.43 ing into the CSF. As in plasma, the principal fibrinolytic

A B
Figure 70-1  A previously healthy 43-year-old woman presented comatose after sudden collapse due to spontaneous intraventricular
bleeding from what proved to be a suprasellar craniopharyngioma. A, CT scan; B, MR image. She made a reasonable recovery following
ventriculoperitoneal shunting and transcallosal tumor debulking.

A B C
Figure 70-2  A 71-year-old woman presented obtunded and paralyzed on the left side of her body from a right lentiform intracerebral
hemorrhage that extended into the ventricular system. See Figure 70-6 for follow-up.
 INTRAVENTRICULAR HEMORRHAGE 1351

A B
Figure 70-3  A 41-year-old man presented comatose after complaining of a sudden severe headache. CT showed a diffuse subarachnoid
hemorrhage from what appeared to be rupture of a right posterior communicating artery aneurysm that bled through the right temporal horn
into the lateral ventricular system. The patient deteriorated and died several days later from raised intracranial pressure.

A B C

D E
Figure 70-4  A 56-year-old man presented comatose after a sudden collapse. A, A ruptured anterior communicating artery was treated
with endovascular coiling. (The patient had a second, small, right middle cerebral artery aneurysm that was not treated.) B and C, CT scan-
ning the next day showed a persistent panventricular hemorrhage that was treated with a single dose of 4 mg of rt-PA via the ventriculostomy
catheter. (See text for protocol details.) D and E, CT scans performed 2 days later demonstrate considerable clearance of ventricular clots,
and the patient went on to make a good clinical recovery.
1352 THERAPY

enzyme in the CSF is plasmin, carried into the ventricles ventricular system, and communicating hydrocephalus
in its precursor form, plasminogen, as a normal blood may develop more gradually or even in a delayed fashion
constituent. It is converted to its active form by tissue- because of obstruction and then scarring of the arachnoid
type plasminogen activator (t-PA). Tissue-type plasmino- granulations from blood elements carried to them by CSF
gen activator is released from the endothelium of small flow. The risk of hydrocephalus correlates with the sever-
vessels in the meninges and ependyma, and leukocytes ity of IVH and is greater if there is blood in the third or
and platelets within the ventricular thrombi are addi- fourth ventricles or if there is associated SAH. In sponta-
tional sources of plasminogen activator enzymes. These neous supratentorial ICH, secondary IVH correlates with
various activators diffuse into clot, bind to fibrin, and acti- the presence of acute hydrocephalus and poor outcome.52
vate plasminogen incorporated into the coagulum. The Acute hydrocephalus is seen in roughly 15% of patients
degree of fibrinolytic activity in “activated” CSF is meager with ruptured aneurysms, and its presence is also signifi-
relative to plasma, but is proportional to the volume of cantly related to the presence of IVH.53
blood clot volume. It is also balanced by the presence of
inhibitors also released into the CSF by inflamed lepto-
Diagnosis
meninges.45 Changes in CSF coagulation and fibrinolysis
have been studied in the context of SAH and are probably IVH is diagnosed with CT, and scoring systems have been
similar to changes following IVH.46 devised to quantify the extent of IVH seen on CT scan
The resolution of intraventricular blood clot appears to (Table 70-1). Clearly, clinical condition and prognosis
follow first-order kinetics, such that the daily percentage are more closely related to ventricular distension, associ-
rate of clot breakdown and clot half-life is constant and ated parenchymal damage, and the underlying cause of
the absolute amount of clot broken down per day rises bleeding.
with increasing IVH volume.47 The clearance of erythro- If CT scanning shows IVH secondary to a deep tha-
cytes from CSF is accomplished by several mechanisms. lamic or ganglionic parenchymal hemorrhage in an adult,
The first is hemolysis, which commences within hours and especially an older person, a small vessel cause can
and reaches a plateau 2 to 10 days after IVH, depending usually be assumed, and further investigation is not man-
on the size of the hemorrhage. Another is phagocytosis by datory. Similarly, if the primary hemorrhage is lobar and
macrophages, which occurs both in the leptomeninges is strongly suspected on clinical grounds to be related
irritated by blood and in arachnoid granulations engorged to a bleeding disorder, amyloid angiopathy, or conver-
with erythrocytes. sion of a cardioembolic infarction, angiography is again
unwarranted. If, after these considerations, the underly-
Clinical Features ing cause of IVH remains uncertain, angiography, MRI,
or both are indicated, especially if thrombolytic therapy
Spontaneous and primary IVH manifests as sudden head- (discussed in the next section) is being considered.
ache, vomiting, and sometimes altered mental status.5,48 Vascular imaging is recommended for any patient with
A generalized seizure may occur, but without any sig- primary IVH of no apparent cause and for any patient
nificant associated ICH, focal signs are generally absent. younger than 45 years who has an IVH.6,48,54 In a 2008
Symptoms from even a large IVH can sometime be sur- review, nearly 60% of patients with primary IVH had
prisingly minimal, provided that the ventricles have not positive angiographic findings of a bleeding source, and
become distended and ICP remains within normal limits. the two most common causes of primary IVH were AVMs
The total volume of CSF in adults is approximately 150 and aneurysms.48
mL, and the normal ventricular volume is only 20 to 30
mL. Acute fourth ventricular distension after aneurysm Treatment
or AVM rupture causing brainstem compression is asso-
ciated with rapid and advanced neurologic deterioration Management is directed at any identified underlying
and with sudden death. cause of IVH (e.g., aneurysm repair, AVM or tumor exci-
With secondary IVH, presenting symptoms are usu- sion, blood pressure control, correction of bleeding dis-
ally due to the associated ICH or SAH, and the nature and order) and external ventricular drainage to relieve any
magnitude of the symptoms and signs correspond to the associated hydrocephalus and help manage raised ICP.
location and size of the hemorrhage. Surgical evacuation through a frontal corticotomy of lat-
Symptomatic vasospasm of the anterior and middle eral ventricles packed with blood clot after aneurysm
cerebral arteries after an AVM-related IVH has been
described,49,50 but the complication is exceptional after
hemorrhage restricted to the ventricles. Delayed-onset TABLE 70-1  GRADING SYSTEM FOR SEVERITY
cerebral vasospasm after aneurysm rupture depends on OF INTRAVENTRICULAR HEMORRHAGE*
thick blood clots deposited in the basal subarachnoid cis-
terns and left in prolonged contact with the adventitial Score Criterion
surfaces of arteries. The presence of thick subarachnoid 1 Less than half of ventricle filled with blood
hematomas along with blood clots also in both lateral ven- 2 More than half of ventricle filled with blood
tricles may predict an especially high risk of delayed cere- 3 Ventricle filled and distended with blood
bral ischemia after aneurysm rupture.51 *Third
Noncommunicating hydrocephalus can occur acutely ventricle, fourth ventricle, and each lateral ventricle are scored
separately. All the scores are then summed (maximum total score = 12).
after IVH if clots obstruct CSF drainage within the
 INTRAVENTRICULAR HEMORRHAGE 1353

rupture was judged not to be useful,55 but there has clot clearance and that it does not appear to induce new
been a report of successful fourth ventricle decompres- or repeated hemorrhages.73,75-80 Several reviews have
sion.56 Surgery for IVH decompression is not generally reached the same conclusions.81,82
recommended. Urokinase has been replaced by rt-PA for routine
A regular problem with ventriculostomy for IVH is clinical use and is the agent being tested in (Clot Lysis:
catheter occlusion with blood clot, necessitating irriga- Evaluating Accelerated Resolution of Intraventricular
tion or replacement of the catheter. With obstruction Hemorrhage (CLEAR IVH) trial, an ongoing (at the time
of the foramen of Monro, bilateral ventricular drainage of this writing in April 2008) randomized controlled trial
tubes are sometimes necessary. Infection becomes a risk comparing simple external ventricular drainage with IVF
among patients with IVH in whom prolonged drainage (with drainage) in patients with spontaneous, hyperten-
is required.57 In addition, ventricular drainage alone has sive ICH complicated by obstructive IVH.83 This study
a limited ability to relieve cerebral compression due to hopes to determine whether IVF has an impact on clinical
intraventricular blood clots themselves. outcome, clot reduction, and bleeding events in patients
Intraventricular clot breakdown using fibrinolytic with spontaneous ICH with extension in the ventricles
enzymes showed promise in animal models of IVH, resulting in ventricular obstruction.
speeding clearance of ventricular clots, restoring ventric- On the basis of current evidence, IVF can be consid-
ular size, preventing hydrocephalus, and reducing CSF ered for patients with large IVHs that expand and occlude
outflow resistance.58-62 Reports and case series of intra- the ventricular system but without large parenchymal
ventricular fibrinolysis (IVF) in human patients followed, hematomas or clinical conditions that strongly predict
consisting of either injections or infusions of urokinase unfavorable outcome regardless of the IVH. Fibrinolytic
or recombinant t-PA (rt-PA) through external ventricular treatment is not likely to be helpful in patients with
drainage catheters for IVH resulting from aneurysm and extensive deep or dominant brain destruction, those with
AVM rupture, chronic hypertension, ventricular catheter severely elevated ICP, or those with rapidly failing brain-
insertion, trauma, and germinal matrix hemorrhage in stem activity.
the newborn.63-74 Although the type, dose, and duration Our protocol is to begin treatment after CT confirma-
of fibrinolytic treatment varied, these preliminary studies tion of results of uncomplicated surgery for aneurysm or
indicated that IVF accelerated IVH clearance and seemed AVM repair (if applicable) and satisfactory placement of
to have little risk. One case series of mostly aneurysm a ventricular drain catheter. A 2- to 4-mg (1 mg/mL) dose
patients also suggested rt-PA clearance of IVH helped con- of rt-PA is given slowly through the ventricular catheter
trol elevated ICP, especially in younger patients with little with frequent checks of ICP to ensure that it does not
intracranial compliance or those in poor neurologic con- reach dangerous levels, which would compromise cere-
dition due to severe bleeding.65 bral perfusion pressure. If the patient tolerates only a por-
Cohort studies have since compared IVF with exter- tion of the 4-mg dose, the remainder can be given 1 hour
nal ventricular drainage alone (Table 70-2). All have con- later. Care must be taken to ensure that the volume of
firmed that IVF is effective in accelerating intraventricular rt-PA dosage exceeds the CSF-filled tubing “dead” space

TABLE 70-2  COMPARISON STUDIES OF INTRAVENTRICULAR FIBRINOLYSIS WITH EXTERNAL VENTRICULAR DRAINAGE VERSUS
EXTERNAL VENTRICULAR DRAINAGE ALONE
Study, Fibrinolytic
­Population, Year No. Patients Cause of IVH Agent Main Study Results

Coplin et al,75 40 (22 received Hypertensive ICH Urokinase IVF resulted in faster clot clearance, lower mortality
single center, IVF) in most rate, trend to better outcomes
1998
Naff et al,73 20 (16 received Hypertensive ICH Urokinase IVF was associated with better 30-day survival
­multi-center, 2000 IVF, 8 in most than predicted
­randomized)
Findlay & Jacka,76 30 (21 received Aneurysm rupture rt-PA IVF resulted in more rapid ventricular opening,
single-center, IVF) fewer EVD replacements
2004
Naff et al,77 12 (7 random- Hypertensive ICH Urokinase Randomization to IVF (and female gender) favor-
­multi-center, 2004 ized to IVF) ably affected clot resolution rate
Varelas et al,78 20 (10 received Aneurysm rupture rt-PA IVF resulted in faster clot clearance, trend to
single center, IVF) decreased need for shunt placement, better
2005 outcome
Torres et al,79 single 28 (14 received Hypertensive ICH Urokinase IVF resulted in faster clot clearance, fewer catheter
center, 2008 IVF) obstructions, improved outcome
Huttner et al,80 135 (27 received Hypertensive ICH rt-PA IVF hastened clot clearance, reduced the need for
single center, IVF) repeated EVD exchanges and permanent shunt-
2008 ing, but did not influence long-term outcome
EVD, external ventricular drainage; ICH, intracerebral hemorrhage; IVF, intraventricular fibrinolysis; IVH, intraventricular hemorrhage; rt-PA, recombinant
tissue-type plasminogen activator.
1354 THERAPY

A B

C D
Figure 70-5  A 32-year-old cocaine abuser presenting with a severe headache and double vision was found to have third and lateral
ventricular bleeding, along with global cerebral atrophy on CT scan (A and B). Cerebral angiography findings were normal. Following
administration of 4 mg of intraventricular recombinant tissue-type plasminogen activator (rt-PA), the ventricles cleared and it became appar-
ent that there was an underlying midbrain hemorrhage in the tectum (C and D). The patient was left with a permanent paralysis of upgaze,
skew deviation, and a right trochlear nerve palsy (components of Parinaud’s syndrome), resulting in constant diplopia.

between injection port and ventricle to ensure that the another made a good recovery. Several examples of rt-PA
rt-PA reaches the ventricles. treatment are shown in Figures 70-5 and 70-6.
Following rt-PA injection the ventricular drain is closed
for 1 hour and is then opened to drain against a pressure
Prognosis
gradient of 1 to 2 cm (above the level of the external
auditory canal) for 1 hour. The drain is then opened and The presence of IVH does not necessarily portend a poor
closed during alternating hours for the next 24 hours. CT prognosis in every patient, as was once thought. Even
scanning is performed daily for the first several days, and quite large primary IVHs can be associated with a good
additional rt-PA can be given if necessary, the goal being clinical condition and good outcome.86,87 However, sec-
to open ventricular pathways, restore normal ventricular ondary IVHs associated with large subarachnoid hemor-
size, reduce intracranial hypertension, and maintain cath- rhage or ICH or anticoagulant treatment are associated
eter patency. Complete clearance of clot settled in depen- with poorer neurologic condition on presentation and a
dent parts of the lateral ventricles is not necessary. worse outcome.88-90 Massive IVH that produces fourth
We have administered IVF after endovascular coil- ventricular distension and periventricular cerebral com-
ing of ruptured aneurysms without subsequent bleeding pression is an especially ominous sign associated with
complications (see Fig. 70-4), a therapeutic maneuver early death (Fig. 70-7).38
reported by others in several patients.84,85 Interference of Patients with large IVHs who survive hemorrhage with-
aneurysm thrombosis in the coil mass by the administra- out vital brain destruction are potential candidates for
tion of rt-PA and the potential risk of aneurysm rebleed- IVF. Intraventricular fibrinolysis helps maintain ventricu-
ing remains a concern. Risks and potential benefits must lostomy blockage with blood clot, promotes rapid IVH
be taken into account under these circumstances. All of clearance, and, we believe, facilitates ICP management, all
the patients described in the literature who had aneu- of which are of great practical help in the intensive care
rysm coiling followed by IVF had high-grade aneurysm management of patients with severe IVH. It is not cur-
ruptures with massive IVH, and one of our own patients rently known whether IVF by itself improves long-term
went on to die from severe subarachnoid hemorrhage; clinical outcome, but this is a subject of ongoing study.
 INTRAVENTRICULAR HEMORRHAGE 1355

A B C
Figure 70-6  Following two consecutive days of intraventricular fibrinolysis (rt-PA, 4 mg per day via the external ventricular drain), a
71-year-old woman with a right-sided lentiform hemorrhage with intraventricular extension (see Fig. 70-2) had considerable clot clearance
from the ventricular system. A ventriculoperitoneal shunt was not required. She recovered to her baseline cognition but had a permanent left
hemiparesis that prevented her from ambulation.

5. A ngelopoulos M, Gupta SR, Azat KB: Primary intraventricular hem-

orrhage in adults: Clinical features, risk factors, and outcome, Surg
Neurol 44:433–436, 1995.
6. Chang DS, Lin CL, Howng SL: Primary intraventricular hemorrhage
in adult—an analysis of 24 cases, Kao Hsiung I Hsueh Ko Hsueh
Tsa Chih 14:633–638, 1998.
7. Marti-Fabregas J, Piles S, Guardia E, et al: Spontaneous primary
intraventricular hemorrhage: Clinical data, etiology and outcome,
J Neurol 246:287–291, 1999.
8. Taheri SA, Wani MA, Lewko J: Uncommon causes of intraventricu-
lar hemorrhage, Clin Neurol Neurosurg 92-3:195–202, 1990.
9. Bergsneider M, Grazee JG, DeSalles AA: Thalamostriate artery aneu-
rysm within the third ventricle, J Neurosurg 81:463–465, 1994.
10. Hamada J, Hashimoto N, Tskukahara T: Moyamoya disease with
repeated intraventricular hemorrhage due to aneurysm rupture,
J Neurosurg 80:328–331, 1994.
11. Newman P, Al-Menar A: Intraventricular hemorrhage in pregnancy
due to moyamoya disease, J Neurol Neurosurg Psychiatry 64:686,
1998.
12. Larrazabal R, Pelz D, Findlay JM: Endovascular treatment of a len-
ticulostriate artery aneurysm with N-butyl cyanoacrylate, Can J
Neurol Sci 28:256–259, 2001.
13. Szabo K, Sommer A, Gass A, et al: Rapid resorption of intraven-
tricular hemorrhage after thrombolytic therapy of ischemic stroke,
Cerebrovasc Dis 12:144, 2001.
14. Gebel JL, Sila CA, Sloan MA, et al: Thrombolysis-related intra-­
cranial hemorrhage: A radiographic analysis of 244 cases from the
GUSTO-1 trial with clinical correlation, Stroke 29:563–569, 1998.
15. Toffol GJ, Biller J, Adams HP Jr: Nontraumatic intracerebral hemor-
rhage in young adults, Arch Neurol 44:483–485, 1987.
16. L indboe CF, Stolt-Nielsen A, Dale LG: Hemorrhage in a highly vas-
Figure 70-7  A spontaneous cerebellar hemorrhage in a cularized subependymoma of the septum pellucidum: Case report,
31-­year-old man with intraventricular extension resulted in rapid Neurosurg 31:741–745, 1992.
progression to brain death. 17. Matsushima M, Yamamoto T, Motomochi M, Ando K: Papilloma and
venous angioma of the choroid plexus causing primary intraven-
tricular hemorrhage, J Neurosurg 39:666–670, 1973.
18. Lang I, Jackson A, Strang FA: Intraventricular hemorrhage caused
REFERENCES by intraventricular meningioma: CT appearance, AJNR Am J Neu-
roradiol 6:1378–1381, 1995.
1. Darby DG, Donnan GA, Saling MA, et al: Primary intraventricular 19. Murai Y, Yoshida D, Ikeda Y, et al: Spontaneous intraventricular
hemorrhage: Clinical and neuropsychological findings in a pro- hemorrhage caused by lateral ventricular meningioma—case
spective stroke series, Neurology 38:68–75, 1988. report, Neurol Med Chir (Tokyo) 36:586–589, 1996.
2. Pia HW: The surgical treatment of intracerebral and intraventricu- 20. Challa VR, Richards F II, Davis CH Jr: Intraventricular hemorrhage
lar haematomas, Acta Neurochir 27:149–164, 1972. from pituitary apoplexy, Surg Neurol 16:360–361, 1981.
3. L ittle JR, Blomquist GA Jr, Ethier R: Intraventricular hemorrhage in 21. Okamura A, Goto S, Sato K, Ushio Y: Central neurocytoma with
adults, Surg Neurol 8:143–149, 1977. hemorrhagic onset, Surg Neurol 43:252–255, 1995.
4. Donauer E, Reif J, Al-Khalaf E, et al: Intraventricular haemorrhage 22. Graziani N, Dufour H, Figarella-Branger D, et al: Suprasellar
caused by aneurysms and angiomas, Acta Neurochir 122:23–31, ­g ranular-cell tumor, presenting with intraventricular haemorrhage,
1993. Br J Neurosurg 9:97–102, 1995.
1356 THERAPY

23. Mandybur TI: Intracranial hemorrhage caused by metastatic 48. Flint AC, Roebken A, Singh V: Primary intraventricular hemor-
tumors, Neurology 27:650–655, 1977. rhage: yield of diagnostic angiography and clinical outcome, Neu-
24. Young WB, Lee KP, Pessin MS: Prognostic significance of ventricu- rocrit Care 8:330–336, 2008.
lar blood in supratentorial hemorrhage: A volumetric study, Neu- 49. Yanaka K, Hyodo A, Tsuchida Y, et al: Symptomatic cerebral vaso-
rology 40:616–619, 1990. spasm after intraventricular hemorrhage from ruptured arteriove-
25. Juvela S, Hillbom M, Palomäki H: Risk factors for spontaneous intra- nous malformation, Surg Neurol 38:63–67, 1992.
cerebral hemorrhage, Stroke 26:1558–1564, 1995. 50. Maeda K, Kurita H, Nakamura T, et al: Occurrence of severe vaso-
26. Broderick JP, Brott TG, Duldner JE, et al: Volume of intracerebral spasm following intraventricular hemorrhage from an arteriove-
hemorrhage: A powerful and easy-to-use predictor of 30-day mor- nous malformation: Report of two cases, J Neurosurg 87:436–439,
tality, Stroke 24:987–993, 1993. 1997.
27. Ruscalleda J, Peiró A: Prognostic factors in intraparenchymatous 51. Classen J, Bernardini GL, Kreiter K, et al: Effect of cisternal and
hematoma with ventricular hemorrhage, Neuroradiology 28:34– ventricular blood on risk of delayed cerebral ischemia after sub-
37, 1986. arachnoid hemorrhage: The Fisher Scale revisited, Stroke 32:2012–
28. Hallevi H, Albright KC, Aronowski J, et al: Intraventricular hemor- 2020, 2001.
rhage: Anatomic relationships and clinical implications, Neurology 52. Diringer MN, Edwards DF, Zazulia AR: Hydrocephalus: A previ-
70:848–852, 2008. ously unrecognized predictor of poor outcome from supratentorial
29. Phan TG, Koh M, Vierkant RA, et al: Hydrocephalus is a determi- intracerebral hemorrhage, Stroke 29:1352–1357, 1998.
nant of early mortality in putaminal hemorrhage, Stroke 31:2157– 53. Mohr G, Ferguson G, Khan M, et al: Intraventricular hemorrhage
2162, 2000. from ruptured aneurysm: Retrospective analysis of 91 cases, J Neu-
30. L iliang PC, Liang CL, Lu CH, et al: Hypertensive caudate hemor- rosurg 58:482–487, 1983.
rhage prognostic predictor, outcome, and role of external ventricu- 54. Graeb DA, Robertson WD, Lapointe JS, et al: Computed tomo-
lar drainage, Stroke 32:1195–1200, 2001. graphic diagnosis of intraventricular hemorrhage, Radiology
31. Bhattathiri PS, Gregson B, Prasad KS, et al: Intraventricular hem- 143:91–96, 1982.
orrhage and hydrocephalus after spontaneous intracerebral hem- 55. Shimoda M, Oda S, Shibata M, et al: Results of early surgical evacua-
orrhage: Results from the STICH trial, Acta Neurochir Suppl tion of packed intraventricular hemorrhage from aneurysm rupture
96:65–68, 2006. in patients with poor-grade subarachnoid hemorrhage, J Neuro-
32. Huttner HB, Kohrmann M, Berger C, et al: Influence of intraven- surg 91:408–414, 1999.
tricular hemorrhage and occlusive hydrocephalus on the long-term 56. Lagares A, Putman CM, Ogilvy CS: Posterior fossa decompression
outcome of treated patients with basal ganglia hemorrhage: A case- and clot evacuation for fourth ventricle hemorrhage after aneurys-
control study, J Neurosurg 105:412–417, 2006. mal rupture: Case report, Neurosurgery 49:208–211, 2001.
33. Findlay JM: Intraventricular hemorrhage, Neurosurg Q 10:182–195, 57. Mayhall CG, Archer NH, Lamb VA, et al: Ventriculostomy-related
2000. infections: A prospective epidemiologic study, N Engl J Med
34. Vale FL, Bradley EL, Fisher WS III: The relationship of subarachnoid 310:553–559, 1984.
hemorrhage and the need for postoperative shunting, J Neurosurg 58. Pang D, Sclabassi RJ, Horton JA: Lysis of intraventricular blood clot
86:462–466, 1997. with urokinase in a canine model: Part 1: Canine intraventricular
35. Graff-Radford NR, Torner J, Adams HP Jr, Kassell NF: Factors asso- blood cast model, Neurosurgery 19:540–546, 1986.
ciated with hydrocephalus after subarachnoid hemorrhage, Arch 59. Pang D, Sclabassi RJ, Horton JA: Lysis of intraventricular blood clot
Neurol 46:744–752, 1989. with urokinase in a canine model: Part 2: In vivo safety study of
36. de Oliveira JG, Beck J, Setzer M, et al: Risk of shunt-dependent intraventricular urokinase, Neurosurgery 19:547–552, 1986.
hydrocephalus after occlusion of ruptured intracranial aneurysms 60. Mayfrank L, Kissler J, Raoofi R, et al: Ventricular dilatation in exper-
by surgical clipping or endovascular coiling: A single-institution imental intraventricular hemorrhage in pigs: Characterization of
series and meta-analysis, Neurosurgery 61:924–934, 2007. cerebrospinal fluid dynamics and the effects of fibrinolytic treat-
37. Inagawa T, Hirano A: Ruptured intracranial aneurysms: An autopsy ment, Stroke 28:141–148, 1997.
study of 133 patients, Surg Neurol 33:117–123, 1990. 61. Brinker T, Seifert V, Stolke D: Effect of intrathecal fibrinolysis on
38. Ruelle A, Cavazzani P, Andrioli G: Extracranial posterior inferior cerebrospinal fluid absorption after experimental subarachnoid
cerebellar artery aneurysm causing isolated intraventricular hem- hemorrhage, J Neurosurg 74:789–793, 1991.
orrhage: A case report, Neurosurgery 23:774–777, 1988. 62. Brinker T, Seifert V, Dietz H: Subacute hydrocephalus after experi-
39. Schievink WI, Wijdicks EFM, Parisi JE, et al: Sudden death from mental subarachnoid hemorrhage: Its prevention by intrathecal
aneurysmal subarachnoid hemorrhage, Neurology 45:871–874, fibrinolysis with recombinant tissue plasminogen activator, Neuro-
1995. surgery 31:306–312, 1992.
40. Shapiro SA, Campbell RL, Scully T: Hemorrhagic dilation of the 63. Shen PH, Matsuoka Y, Kawajiri K, et al: Treatment of intraventricu-
fourth ventricle: An ominous predictor, J Neurosurg 80:805–809, lar hemorrhage using urokinase, Neurol Med Chir (Tokyo) 30:329–
1994. 333, 1990.
41. Mohr G, Ferguson G, Khan M, et al: Intraventricular hemorrhage 64. Todo T, Usui M, Takakura K: Treatment of severe intraventricular
from ruptured aneurysm: Retrospective analysis of 91 cases, J Neu- hemorrhage by intraventricular infusion of urokinase, J Neurosurg
rosurg 58:482–487, 1983. 74:81–86, 1991.
42. Heuer GG, Smith MJ, Elliott JP, et al: Relationship between intracra- 65. Findlay JM, Grace MGA, Weir BKA: Treatment of intraventricular
nial pressure and other clinical variables in patients with aneurys- hemorrhage with tissue plasminogen activator, Neurosurgery
mal subarachnoid hemorrhage, J Neurosurg 101:408–416, 2004. 32:941–947, 1993.
43. Rosengart AJ, Schultheiss KE, Tolentino J, et al: Prognostic factors 66. Findlay JM, Weir BKA, Stollery DE: Lysis of intraventricular hema-
for outcome in patients with aneurysmal subarachnoid hemor- toma with tissue plasminogen activator, J Neurosurg 74:803–807,
rhage, Stroke 38:2315–2321, 2007. 1991.
44. Hartmann A, Mast H, Mohr JP, et al: Morbidity of intracranial hem- 67. Mayfrank L, Lippitz B, Groth M, et al: Effect of recombinant tissue
orrhage in patients with cerebral arteriovenous malformation, plasminogen activator on clot lysis and ventricular dilatation in the
Stroke 29:931–934, 1998. treatment of severe intraventricular hemorrhage, Acta Neurochir
45. Findlay JM, Weir BKA, Kanamaru K, et al: Intrathecal fibrinolytic 122:32–38, 1993.
therapy after subarachnoid hemorrhage: Dosage study in a primate 68. R hode V, Schaller C, Hassler WE: Intraventricular recombinant
model and review of the literature, Can J Neurol Sci 16:28–40, 1989. tissue plasminogen activator for lysis of intraventricular haemor-
46. I keda K, Asakura H, Futami K, et al: Coagulative and fibrinolytic rhage, J Neurol Neurosurg Psychiatry 58:447–451, 1995.
activation in cerebrospinal fluid and plasma after subarachnoid 69. A kdemir H, Selcuklu A, Pasaoglu A, et al: Treatment of severe intra-
hemorrhage, Neurosurgery 41:344–350, 1997. ventricular hemorrhage by intraventricular infusion of urokinase,
47. Naff NJ, Williams MA, Rigamonti D, et al: Blood clot resolution in Neurosurg Rev 18:95–100, 1995.
human cerebrospinal fluid: Evidence of first-order kinetics, Neuro- 70. R ainov NG, Burkert WL: Urokinase infusion for severe intraven-
surgery 49:614–621, 2001. tricular haemorrhage, Acta Neurochir 134:55–59, 1995.
 INTRAVENTRICULAR HEMORRHAGE 1357

71. Grabb PA: Traumatic intraventricular hemorrhage treated with 81. Nieuwkamp DJ, de Gans K, Rinkel GJE, et al: Treatment and out-
intraventricular recombinant-tissue plasminogen activator: Techni- come of severe intraventricular extension in patients with sub-
cal case report, Neurosurgery 43:966–969, 1998. arachnoid hemorrhage: A systematic review of the literature,
72. Goh KY, Poon WS: Recombinant tissue plasminogen activator for J Neurol 247:117–121, 2000.
the treatment of spontaneous adult intraventricular hemorrhage, 82. Engelhard HH, Andrews CO, Slavin KV, et al: Current management
Surg Neurol 50:526–531, 1998. of intraventricular hemorrhage, Surg Neurol 60:15–21, 2003.
73. Naff NJ, Carhuapoma JR, Williams MA, et al: Treatment of intra- 83. Johns Hopkins University: CLEAR IVH: Clot Lysis: Evaluating Accel-
ventricular hemorrhage with urokinase: Effects on 30-day survival, erated Resolution of Intraventricular Hemorrhage (IVH). Available
Stroke 31:841–847, 2000. at www.clearivh.com.
74. Haines SJ, Lapointe M: Fibrinolytic agents in the management of 84. A zmi-Ghadimi H, Heary RF, Farkas JE, et al: Use of intraventricular
post hemorrhagic hydrocephalus in preterm infants: The evidence, tissue plasminogen activator and Guglielmi detachable coiling for
Childs Nerv Syst 15:226–234, 1999. the acute treatment of casted ventricles from cerebral aneurysm
75. Coplin WD, Vinas FC, Agris JM, et al: A cohort study of the safety hemorrhage: Two technical case reports, Neurosurgery 50:421–
and feasibility of intraventricular urokinase for nonaneurysmal 424, 2002.
spontaneous intraventricular hemorrhage, Stroke 29(8):1573–1579, 85. Hall B, Parker D Jr, Carhuapoma JR: Thrombolysis for intraventricu-
1998. lar hemorrhage after endovascular aneurysmal coiling, Neurocrit
76. Findlay JM, Jacka MJ: Cohort study of intraventricular thromboly- Care 3:153–156, 2005.
sis with recombinant tissue plasminogen activator for aneurysmal 86. Verma A, Maheshwari MC, Bhargava S: Spontaneous intraventricu-
intraventricular hemorrhage, Neurosurgery 55(3):532–537, 2004. lar haemorrhage, J Neurol 234:233–236, 1987.
77. Naff NJ, Hanley DF, Keyl PM, et al: Intraventricular thrombolysis 87. Roos YB, Hasan D, Vermeulen M: Outcome in patients with large
speeds blood clot resolution: Results of a pilot, prospective, ran- intraventricular haemorrhages: A volumetric study, J Neurol Neu-
domized, double-blind, controlled trial, Neurosurgery 54(3): rosurg Psychiatry 58:622–624, 1995.
577–584, 2004. 8 8. De Weerd AW: The prognosis of intraventricular hemorrhage,
78. Varelas PN, Rickert KL, Cusick J, et al: Intraventricular hemorrhage J Neurol 222:45–51, 1979.
after aneurysmal subarachnoid hemorrhage: Pilot study of treat- 89. Juvela S: Risk factors for impaired outcome after spontaneous intra-
ment with intraventricular tissue plasminogen activator, Neurosur- cerebral hemorrhage, Arch Neurol 52:1193–2000, 1995.
gery 56(2):205–213, 2005. 90. Sjoblom L, Hårdemark HG, Lindgren A, et al: Management of prog-
79. Torres A, Plans G, Martino J, et al: Fibrinolytic therapy in spontane- nostic features of intracerebral hemorrhage during anticoagulant
ous intraventricular haemorrhage: Efficacy and safety of the treat- therapy: A Swedish multicenter study, Stroke 32:2567–2574, 2001.
ment, Br J Neurosurg 22(2):269–274, 2008.
80. Huttner HB, Tognoni E, Bardutzky J, et al: Influence of intra-
ventricular fibrinolytic therapy with rt-PA on the long-
term outcome of treated patients with spontaneous basal
ganglia hemorrhage: A case-control study, Eur J Neurol 15(4):
342–349, 2008.