INTRODUCTION — Intraventricular hemorrhage (IVH) confined to the ventricular system within the brain is uncommon, accounting for only about 3 percent of all spontaneous intracranial hemorrhage [1]. IVH more commonly occurs in the setting of intracerebral hemorrhage or subarachnoid hemorrhage.

The assessment of the patient with IVH focuses on identifying the underlying cause of the hemorrhage, which may have significant treatment implications. Common to patients with IVH, regardless of etiology, is a risk for sudden and potentially fatal obstructive hydrocephalus, requiring acute clinical decision-making regarding the use of external ventricular drainage and other interventions.

This topic discusses the causes, clinical presentation, diagnosis, and treatment of IVH. Intracerebral, subarachnoid, subdural, and epidural hemorrhage are discussed separately:

●(See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis".)

●(See "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis".)

●(See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis".)

●(See "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis".)

●(See "Subdural hematoma in adults: Etiology, clinical features, and diagnosis".)

●(See "Subdural hematoma in adults: Management and prognosis".)

●(See "Intracranial epidural hematoma in adults".)

IVH in the newborn is also discussed separately. (See "Germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) in the newborn: Pathogenesis, clinical presentation, and diagnosis" and "Germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) in the newborn: Prevention, management, and complications".)

EPIDEMIOLOGY AND DEFINITIONS — Primary IVH refers to bleeding confined to the ventricular system within the brain. Primary IVH is uncommon, accounting for only about 3 percent of all spontaneous intracerebral hemorrhage [1]. The following demographic characteristics were reported in a 2008 review of published cases series of primary IVH [2]:

●The median age is 55 years (range 9 to 91 years).

●Males and females are equally represented.

●Half of patients have a history of hypertension.

Secondary IVH refers to the more common occurrence of IVH in the setting of intracerebral hemorrhage or subarachnoid hemorrhage (secondary IVH). The epidemiology of intracerebral hemorrhage and subarachnoid hemorrhage is discussed separately. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis" and "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis".)

ETIOLOGY — IVH most commonly occurs as a secondary phenomenon when parenchymal or intracerebral hemorrhage (ICH) ruptures into the ventricular space or when subarachnoid hemorrhage (SAH) extends into the ventricles. IVH is estimated to complicate 40 to 60 percent of ICH and 10 percent of SAH cases [3-5]. In one retrospective review, warfarin therapy was associated with IVH risk, volume at presentation, and subsequent expansion in patients with deep or lobar ICH [6]. The underlying causes of ICH and SAH are discussed separately. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis" and "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis" and "Nonaneurysmal subarachnoid hemorrhage".)

IVH can also complicate closed head injury. Usually, this is in the setting of other traumatic brain injury, including contusion and traumatic SAH; isolated IVH is a relatively rare complication of head trauma [7-9].

Primary IVH is uncommon; in consequence, studies estimating the frequency of various etiologies have been limited. Retrospective case series derived from tertiary referral centers are subject to ascertainment bias. Further, definitions of primary IVH have varied among different authors and studies. While most limit their use of the term to hemorrhages entirely localized within the ventricle, others have included hemorrhages that originate within 15 mm of the ependymal surface [10]. The latter criteria invariably classify thalamic, caudate, and medial putaminal bleeds (usually secondary to chronic hypertension) associated with IVH as primary IVH.

Among series that more strictly limit the definition of IVH, vascular malformations are the most frequently identified cause of primary IVH. In small case series, vascular malformations have been identified in 14 to 58 percent of patients with primary IVH [2,10-15]. Reported causes of primary IVH include:

●Vascular malformations (usually arteriovenous malformations or arteriovenous fistulae) [1,2,10-19].

●Intraventricular tumors (papilloma, neurocytoma, meningioma, metastases, astrocytoma, ependymoma) [11,20-26].

●Intraventricular aneurysms developing within the distal lenticulostriate or choroidal arteries (occasionally reported in association with Moyamoya disease) [10,16,22,27]. Occasionally aneurysms of the anterior communicating artery, posterior inferior cerebellar artery, or basilar tip rupture into the ventricles without other overt subarachnoid blood [2,10,14].

●Moyamoya disease [1,2,16,22,28-31]. (See "Moyamoya disease: Etiology, clinical features, and diagnosis".)

●Coagulopathies, acquired or inherited [2,10,12,29,32,33].

●Pituitary apoplexy [34].

●Vasculitis [35].

●Fibromuscular dysplasia [10].

●Sympathomimetic abuse [36,37].

In approximately 20 to 50 percent of cases (depending in part on the intensity of the investigation), no cause is identified [11,12,16,33]. About half of these patients have chronic hypertension; this is believed, but not known, to cause primary IVH in the same way it is understood to cause ICH. It is speculated that some patients with IVH may have had a small hypertensive intraparenchymal hemorrhage, too small to see on computed tomography or magnetic resonance imaging, which arises in proximity to the ventricular system and produces IVH as its primary manifestation. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Pathogenesis and etiologies'.)

CLINICAL FEATURES

Clinical presentation — Patients with secondary IVH present with clinical features typical of intracerebral hemorrhage or subarachnoid hemorrhage. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis" and "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis".)

Patients with primary IVH typically present with abrupt headache, often associated with nausea, vomiting, and impaired consciousness (confusion, disorientation) [2,11,33,38]. A minority of patients have frank loss of consciousness at the onset [12]. Symptoms are usually sudden in onset; however, nearly a quarter of patients are reported to have progressive or fluctuating symptoms [11,12]. The degree of neurologic impairment, often measured as the Glasgow Coma Scale (table 1) is an important prognostic indicator. (See 'Prognosis' below.)

Focal neurologic findings are relatively uncommon with primary IVH and most typically involve cranial nerve abnormalities [10]. Such cranial nerve palsies are generally of the "false localizing" type due to stretching across the basilar skull surface and include dysfunction of the sixth and third nerves. Seizures are not common but can occur [1,10,11,17]. Most patients are hypertensive on presentation, and some will have an elevated body temperature or suffer cardiac arrhythmias [12]. Nuchal rigidity is inconsistently present.

The clinical symptoms and signs of IVH reflect a sudden increase in intracranial pressure that results from sudden introduction of blood volume into the intracranial space [39]. In addition to pressure effects, it is speculated that blood products in the cerebrospinal fluid space may affect brain function.

Complications — Patients with primary or secondary IVH are at risk for sudden neurologic deterioration, which may result from obstructive hydrocephalus, recurrent hemorrhage, or other complications [12]:

●Acute obstructive hydrocephalus can result when cerebrospinal fluid circulation is obstructed by blood clots. Patients with blood in the third or fourth ventricle are at most risk of this complication [12]. One-half to two-thirds of patients with IVH have some degree of hydrocephalus on the initial computed tomography scan [2,11,12,15,40]. This can be rapidly fatal and usually requires urgent intervention and insertion of an external ventricular drain [8,39]. (See 'External ventricular drain' below.)

Patients may also develop communicating hydrocephalus as a delayed complication of IVH; this usually presents more gradually. (See 'Prognosis' below.)

●Recurrent hemorrhage or hemorrhage extension occurs in 10 to 20 percent of patients with IVH [12,39]. The highest risk of this is in those with an underlying etiology of vascular malformation or aneurysm or in the setting of a coagulopathy.

●Cerebral vasospasm with ischemia is unusual in cases of primary IVH, but this complication has been described in isolated cases [19,41-43]. In contrast, vasospasm is a common complication of aneurysmal subarachnoid hemorrhage. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis".)

●Medical complications are common in the setting of IVH and may manifest primarily as neurologic deterioration. These include pulmonary embolism, pneumonia and other infections, and electrolyte imbalance. Other medical complications of IVH include cardiovascular instability, deep venous thrombosis, and gastrointestinal bleeding.

DIFFERENTIAL DIAGNOSIS — The presentation of primary IVH overlaps with those of aneurysmal subarachnoid hemorrhage, which because of its implications for urgent diagnostic and therapeutic interventions should be immediately excluded with emergent computed tomography (CT) scan. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis".)

Other etiologies of a headache with sudden onset include cerebral venous thrombosis, cerebral hemorrhage, and ischemic stroke, among others (table 2). A noncontrast head CT will distinguish IVH from these other entities. (See "Overview of thunderclap headache", section on 'Diagnostic evaluation'.)

DIAGNOSTIC EVALUATION

Computed tomography — Noncontrast head computed tomography (CT) is the test of choice to diagnose IVH. CT rapidly and reliably identifies blood within the ventricular system, helps to identify parenchymal intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) associated with the IVH, and also identifies concurrent hydrocephalus.

In patients with suspected primary IVH, close examination of the brain regions surrounding the ventricles (caudate and thalamus, in particular) should be undertaken to exclude an ICH that has ruptured into the ventricles (image 1). If present, the diagnostic evaluation for ICH should be pursued (see "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis"). Similarly, the presence of subarachnoid blood in the basal cisterns or cortical sulci should raise concern for aneurysmal SAH with secondary IVH, and the diagnostic evaluation should be modified accordingly. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis".)

The extent of IVH can be graded by CT. The Graeb score and other scoring systems have been proposed [44-46], but none are widely implemented in clinical practice.

The CT scan should be repeated emergently for any neurologic deterioration to identify recurrent hemorrhage or obstructive hydrocephalus. CT scans are also used to monitor hydrocephalus, particularly during attempts to clamp or remove a drain. Transcranial ultrasonography has been suggested as a possible alternative to serial CT to monitor ventricular size, but the reliability and reproducibility of this technique has yet to be independently validated [47].

Other neuroimaging studies — Other neuroimaging studies are required to define the etiology of a primary IVH. CT does not provide significant information about the cerebral vasculature, and it has limited ability to identify malignancies. In the absence of an obvious precipitant such as trauma or coagulopathy, most patients with primary IVH should undergo further neuroimaging, typically to include magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) or CT angiography (image 2).

If the MRI/MRA or CT angiography is unrevealing, conventional angiography should follow. In a prospective observational study of patients with IVH who underwent catheter angiography, vascular lesions were found in 11 of 17 (65 percent), including 10 patients with arteriovenous malformations, and one with aneurysm [14]. A retrospective review of published case series similarly estimated the yield of angiography at 56 percent, additionally identifying cases of Moyamoya and dural arteriovenous fistula [2]. If the cause of the IVH remains undetermined, it is reasonable in some cases to consider repeat contrast MRI and possibly catheter angiography one to two months following the initial studies after reabsorption of blood products has occurred.

Other tests — Other tests that are important to include are blood clotting studies (prothrombin time, partial thromboplastin time, and platelet count). A toxicology screen should also be considered.

Because electrolyte imbalances can complicate IVH, these should be measured at baseline and followed regularly.

MANAGEMENT

General measures — The treatment of IVH focuses on cessation of bleeding, relieving hydrocephalus, and controlling intracranial pressure (ICP).

Specific therapy aimed at treating the underlying cause should be undertaken (aneurysm or arteriovenous malformation obliteration). Coagulopathies should be corrected. (See "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis" and "Vascular malformations of the central nervous system".)

Patients who have a moderate to severe IVH (impaired alertness and/or extensive intraventricular blood on imaging) should be followed in an intensive care setting. Medical complications are common (eg, pneumonia, deep venous thrombosis, gastrointestinal bleeding, cardiovascular instability, supraventricular tachycardia, hypo- and hypernatremia) and require appropriate monitoring and treatment [1,11]. The head of the bed should be placed at 30 degrees or greater to decrease ICP and reduce the risk of aspiration. Euvolemia should be maintained using isotonic crystalloid solutions, and any elevations in body temperature should be treated aggressively.

For prevention of deep venous thrombosis, mechanical thromboprophylaxis using intermittent pneumatic compression stockings is recommended until a bleeding source has been identified and secured. At that time, antithrombotic therapy can be used. (See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients".)

Because seizures are an infrequent complication of IVH, prophylactic antiseizure medications are not generally used but should be initiated immediately should seizures occur.

Blood pressure management — The optimum blood pressure management in patients with IVH remains undefined. Aggressive blood pressure lowering may minimize the risk of further hemorrhage but must be weighed against the risk of decreased cerebral perfusion in patients with increased ICP. One small pilot trial in 48 patients with IVH found a significantly decreased risk of hemorrhage enlargement in patients who achieved a prespecified goal of lowering mean arterial pressure by 30 mmHg [48].

It seems reasonable to gradually lower elevated blood pressure in patients with normal ICP. Intravenous antihypertensives such as labetalol or nicardipine are typically used, although other agents are acceptable [49]. In the absence of better data specific to IVH, the guidelines outlined for blood pressure management in the setting of ICH seem reasonable. (See "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis", section on 'Blood pressure management'.)

External ventricular drain — An external ventricular drain (EVD) is a small catheter inserted through the skull usually into the lateral ventricle, which is typically connected to a closed collecting device to allow for drainage of cerebrospinal fluid (figure 1). The EVD can also be connected to a transducer that records ICP.

An EVD is indicated for patients with IVH with hydrocephalus and neurologic decline. Rarely, bilateral EVDs may be needed if hemorrhage obstructs the foramen of Monro [50].

The major complications associated with EVD are catheter occlusion due to clotted blood at the intraventricular orifice and infection. The former may be relieved by irrigation or catheter replacement. Symptoms suggestive of infection should prompt cerebrospinal fluid analysis for cell count and culture along with antibiotic therapy as appropriate. Staphylococci are the most common pathogens. Higher rates of bacterial ventriculitis/meningitis occur with longer duration of EVD placement [51]. In one study, those with infection had a mean duration of EVD of 17 days compared with 10 days in those who did not develop infection [51]. Prophylactic catheter change does not clearly improve the risk of infection. (See "Infections of cerebrospinal fluid shunts and other devices".)

Intraventricular thrombolysis — The complications associated with EVD provide a rationale for the use of intraventricular thrombolysis (IVT). Theoretically, instillation of thrombolytic agents into the ventricles can speed clot resolution, avoiding problems with catheter occlusion and shortening the duration of EVD use. It is also possible, although unproven, that more rapid resolution of IVH may decrease the long-term incidence of communicating hydrocephalus [4]. (See 'Prognosis' below.)

A number of case series, observational studies, and small randomized studies have suggested a benefit for IVT, showing increased clot resolution and, in some cases, decreased mortality [3,38,52-62]. The results of randomized clinical trials, on the other hand, have not shown clear benefit:

●The Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR III) trial included 500 patients with IVH and compared treatment with 1 mg alteplase (tPA) or placebo injected through an EVD every eight hours until clot reduction or a clinical endpoint occurred, or 12 doses were given [63]. At 180 days, the primary efficacy outcome of a modified Rankin scale (mRS) score of 3 or less was similar in each group (48 versus 45 percent comparing alteplase to placebo; risk ratio [RR] 1.06, 95% CI 0.88-1.28). Patients who received IVT had a lower mortality (18 versus 29 percent; RR 0.60, 95% CI 0.41-0.86), but a higher rate of severe disability indicated by an mRS score of 5 (17 versus 9 percent; RR 1.99, 95% CI 1.22-3.26). Bleeding complication rates were similar (2 percent) in both groups.

●The Intraventricular Hemorrhage Thrombolysis Trial, a multicenter randomized controlled study, enrolled 48 patients and compared IVT (3 mg tPA) to control (normal saline); each treatment was injected through an EVD every 12 hours until clot reduction or a clinical endpoint occurred (median duration of dosing was 7.5 days for IVT) [64]. The rate of clot resolution was faster for IVT than placebo (18 versus 8 percent per day). Rates of death and ventriculitis were lower than expected and did not differ significantly between treatment groups. Symptomatic bleeding complications were more frequent in the tPA group (23 versus 5 percent), but this did not reach statistical significance. The dose used in this study was higher than that used in the CLEAR III trial.

Bleeding complications are a concern with IVT; recurrent IVH and/or ICH expansion is reported in 8 to 20 percent of patients after IVT [16,39,54,55,64,65]. Typically, patients with known aneurysm or vascular malformation were excluded from early studies of IVT. However, IVT has been used without complication in a few reported cases after the vascular malformation or aneurysm was surgically treated [16,66-68], and even before surgery, in few patients with these lesions [17,69]. Systemic bleeding complications are unlikely to be significantly increased with IVT; in CLEAR IVH, systemic coagulation parameters were similar after administration of tPA and placebo [70].

It is also possible that the risk of bacterial meningitis/ventriculitis may be increased with IVT therapy, but this has not been demonstrated so far [39,54,63,64]. IVT has not been associated with systemic complications [71].

Based on the results of the CLEAR-III trial, we do not recommend routine use of IVT in patients with IVH. One criticism of the CLEAR-III trial is that only a minority of patients experienced substantial IVT removal, suggesting the possibility of benefit with more effective methods for clot removal. Experienced centers that have an established IVT protocol may consider treatment in select cases of large volume IVT refractory to conservative treatment. An example of such a protocol is provided in the table (table 3) [72].

Other approaches — Other reported approaches to prevention and treatment of hydrocephalus in this setting are investigational:

●The use of lumbar drainage combined with IVT was studied in an open-label trial that was stopped early after 30 patients were enrolled; patients with severe IVH with tamponade of the third and fourth ventricles requiring EVD were treated with IVT (control group) or IVT combined with lumbar drainage [73]. The primary endpoint (need for permanent shunt placement of prolonged requirement for cerebrospinal fluid drainage) occurred more frequently in the control versus combined treatment groups (7 out of 16 versus 0 out of 14). In a meta-analysis that included patients in this study as well as an additional 67 patients treated outside of the clinical trial, the combined intervention was associated with an 0.24 absolute risk reduction (95% CI 0.01-0.36) for shunt dependency. This analysis found no significant differences in functional outcomes or cerebrospinal fluid infection rates at 90 days; bleeding complications were less frequent in the combined treatment group (odds ratio 0.4, 95% CI 0.30-0.53).

●A nonrandomized prospective study compared treatment with EVD alone (control group) versus combined EVD and Ommaya reservoir in 60 patients with IVH; all patients received IVT with urokinase [74]. Patients receiving combined treatment received fewer injections of urokinase and had a shorter duration of EVD and improved clot clearance rates.

●A neuroendoscopic approach to extract intraventricular blood is used at some centers and has been studied in small trials [75-77].

●Endoscopic third ventriculostomy has also been used in a number of reported cases to treat acute hydrocephalus related to IVH [78].

●Other centers have reported mixed results with surgical removal of hemorrhage via an open craniotomy [79,80].

PROGNOSIS — The reported in-hospital mortality of IVH varies from 20 to 50 percent [1,2,4,10-12,33,54]. Secondary IVH carries a higher risk of death than primary IVH [15,33,71]. Advanced age, underlying coagulopathy, Glasgow Coma Scale score of 8 or less, and hydrocephalus at presentation are also associated with a higher risk of death [2,12,33,40,71]. While some studies have found that the extent of IVH correlates with prognosis [2,12,40,45], others have not [10,11,15]. The results of one study found that the volume of blood in the third ventricle was a strong and independent predictor of poor outcomes, while the volume of blood in the lateral ventricles, fourth ventricle, or entire ventricular system did not correlate significantly with prognosis [81]. The authors speculated that blood in the third ventricle may affect critical contiguous structures in the midbrain.

Other long-term complications of IVH include:

●Neurocognitive sequelae – Patients with significant IVH are often confused, agitated, and disoriented [1]. These symptoms are often slow to recover and a significant proportion (about half of survivors) are left with disabling cognitive deficits [1,11,16].

●Noncommunicating hydrocephalus – IVH along with a secondary inflammatory/fibrotic response may lead to impaired absorption of cerebrospinal fluid at the arachnoid granulations. This may be manifest by a more subacute decline in cognition, gait, and urinary continence that can occur weeks or later after the initial IVH or as a failure to wean off EVD. Such patients may require permanent ventriculoperitoneal shunt [39]. Approximately 30 to 50 percent of patients with IVH require a shunt placement [16,54,61,67,82-85]. (See "Normal pressure hydrocephalus".)

●Late recurrence of intracerebral hemorrhage or IVH – Recurrent hemorrhage is uncommonly reported after IVH. In one series, 2 of 14 survivors had a subsequent intracerebral hemorrhage [12], while in another series there was no recurrent bleeding in a group of 13 patients after 67 months [11]. The risk of this complication is likely highest in those with an unrecognized and/or unsecured vascular lesion (eg, Moyamoya) [27,86].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults".)

SUMMARY AND RECOMMENDATIONS

●Terminology and etiologies – Intraventricular hemorrhage (IVH) can complicate intracerebral hemorrhage or subarachnoid hemorrhage (secondary IVH). Less commonly, IVH occurs in isolation (primary IVH). The most commonly identified cause of primary IVH is a vascular malformation. Up to half of patients with primary IVH do not have a cause (other than hypertension) identified. (See 'Epidemiology and definitions' above and 'Etiology' above.)

●Clinical features – Patients with IVH usually present with sudden headache, nausea and vomiting, and impaired alertness. (See 'Clinical features' above.)

●Diagnostic evaluation – Patients with a clinical presentation of IVH should undergo immediate noncontrast head computed tomography (CT). The primary purpose is to exclude subarachnoid hemorrhage and to identify the IVH and evaluate its severity and potential for obstructive hydrocephalus. (See 'Computed tomography' above.)

Individuals with primary IVH should have magnetic resonance imaging with magnetic resonance angiography and/or conventional angiography to identify the underlying etiology, particularly a vascular malformation or aneurysm that may require surgical intervention. (See 'Other neuroimaging studies' above.)

●Management – Because acute obstructive hydrocephalus often complicates IVH that involves the third and fourth ventricles, such patients should be closely monitored. When neurologic deterioration occurs, emergent CT scan should be done to exclude the development of obstructive hydrocephalus or recurrent hemorrhage. (See 'Complications' above.)

We recommend external ventricular drainage for neurologic deterioration that occurs with ventricular enlargement. (Grade 1B). (See 'External ventricular drain' above.)

We do not recommend routine use of intraventricular thrombolysis for patients with IVH. Intraventricular thrombolysis can be considered in experienced centers that have established protocols. (See 'Intraventricular thrombolysis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges James Pacelli Jr, MD, who contributed to an earlier version of this topic review.