Introduction

One uncommon type of intracerebral hemorrhage (ICH), the primary intraventricular hemorrhage (PIVH), is a non-traumatic hemorrhage confined to the ventricular system, without any bleeding into the cerebral parenchyma, and its incidence is very rare.1)3)13)19) Sanders described PIVH first, more than a century ago, but few researchers have studied it since then. Prior to the introduction of the computed tomography (CT) scan, knowledge concerning PIVH came from autopsy series, which usually included patients with massive intraventricular hemorrhages who had had poor prognoses, or, more rarely, from a few patients undergoing surgery.

The definition of PIVH is ? hematoma either confined completely within the ventricular system or arising within 15 mm of the ventricular wall.?)13)19) The presence of intraventricular blood is a source of general alarm to neurosurgeons due to the possibility of hydrocephalus and ensuing brain damage. Although small amounts of blood resolve quickly, with no sequelae, the neurosurgeon often encounters a patient who has moderate or severe IVH involving all the ventricles. Relatively little is known about IVH's clinical and imaging features, and even less about its prognosis and mortality predictors. The present study aimed to analyze the clinical and imaging features, etiology, prognosis, and predictors of outcome in PIVH.

Patients and Method

We retrospectively reviewed the clinical data, complementary examinations, outcomes, and computed tomography scans for non-traumatic PIVH occurring between 2002 and 2008 at our institutions. We defined PIVH as ? hematoma caused by non-traumatic factors, either confined completely within the ventricular system or arising within 15 mm of the ventricular wall.?Evaluations of the clinical features included type of onset, presenting type and symptoms, risk factors, and treatment methods. We evaluated all CT scans in detail for the location of blood in the ventricle and for hydrocephalus and reviewed other radiological examinations for any abnormalities.

We evaluated patient outcomes as death directly related to PIVH, survival with a significant neurologic deficit, or survival with minimal neurologic deficits and functional independence. The patients' follow-up periods ranged from 3 month to 2 years.

Results

Patient age ranged from 19-81 years (mean age 55.5 years), with the majority (79%) between the ages of 38 and 71 years. There were 19 patients: 8 females and 11 males. Hematoma sizes ranged between 2 and 42 cc, with 7 under 10 cc, 6 between 10 and 30 cc, and 6 between 30 and 50 cc.

Symptom onset was abrupt in 18 patients and progressive in 1 patient. The most frequent complaint was headache (47%), followed by nausea and vomiting (38%), and 7 patients (38%) suffered from impaired mental statuses, ranging from stupor to semicoma. One patient had cranial nerve abnormalities, consisting of extraocular movement abnormalities (dysconjugate gaze) and facial droop. Motor deficits and abnormal reflexes (hyperreflexia, pathologic reflexes) were present in 2 patients.

Ten patients had elevated blood pressure, with systolic pressure ranging from 150-230 and diastolic pressure from 80-120 mm Hg. Intraventricular hemorrhage was present in the lateral ventricles in 9 scans (7 bilateral, 2 unilateral), while 10 scans showed blood in all ventricles. Of the 9 patients presenting with or developing, hydrocephalus, 8 underwent extraventricular drainage. The remaining 1 was treated medically (Table 1).

The associated risk factors were hypertension in 9 patients, diabetes mellitus in 3 patients, and end stage renal disease, angina, and valvular heart disease in 1 patient each. Angiography was performed on 8 patients. These revealed no aneurysms, definite arteriovenous malformations, or other vascular anomalies except for a suspicious vascular malformation in 1 patient.

Regarding outcomes, 7 (37%) patients died or entered a vegetative state, of whom 4 (58%) had hematomas less than 30 cc and 3 (42%) had hematomas greater than 30 cc. Of the remaining 12, all became functionally independent; 2 (16%) had hematomas greater than 30 cc and 10 (84%) has hematomas less than 30 cc. These results suggest that hematoma volume could correlate with prognosis, but demonstrating this would require a large-scale study needed.

Of the functionally independent patients, 2 had limb weaknesses. Overall, 7 patients (37%) had Glasgow Outcome Scale (GOS) scores of 1 to 2 and 12 (63%) scored 3 to 5. No permanent CSF diversions were performed.

Discussion

1.  Clinical Features

Excluding premature infants, PIVH is very rare and accounts for only 3.1% of all non-traumatic central nervous system hemorrhages. Considering only the adult population,

PIVH is still relatively rare, comprising only 3.1% of all intracranial hemorrhages, and clinicians have reported only a small number of cases.1)9)13)19) Although PIVH is rarely encountered clinically, the real frequency is unknown, as PIVH may in fact be the cause of any sudden death, in particular, any death occurring before the patient reaches the hospital or receives a CT scan. Hospital series may thus be biased toward more benign cases, as current diagnostic imaging capabilities allow the detection of less severe cases. CT can now confirm a diagnosis of PIVH easily and rapidly, depicting blood when it occurs in the ventricular system only, even when it is a small clot in a circumscribed portion of the ventricular system (usually a lateral ventricle).

PIVH affects all age groups, with a mean onset age of 60 years, similar to that reported in other series.13)19) Earlier PIVH diagnoses relied on a sudden onset, with coma or decreased consciousness level, nausea and/or vomiting, nuchal rigidity, severe headache, and bilateral extensor plantar responses, followed by a severe and often fatal outcome.

Nearly all our patients complained of headache. Nausea and/or vomiting, nuchal rigidity, and unilateral or bilateral extensor plantar responses were frequent, but focal motor symptoms and signs were absent or mild. This probably correlated with midline hemorrhage without parenchymal damage, although hematoma's asymmetric features could explain the focal signs. As noted in other studies, hydrocephalus was also a frequent complication in our patients but only occurred when the third or fourth ventricle was involved.

PIVH without a parenchymal component is unusual, carrying an average mortality rate of about 40%. When it occurs in association with aneurysm and a large blood volume causing hydrocephalus, the mortality rate approaches 90%.12)13)19) Unlike intraparenchymal hemorrhage patients, PIVH survivors often left the hospital with no physical disability, which presumably indicates the absence of parenchymal damage. On the other hand, residual cognitive dysfunction is relatively frequent in such patients.

2.  Etiology

The etiology of PIVH is varied, and, in some patients, unknown. Some researchers have argued, by analogy with subarachnoid hemorrhage, that vascular malformations adjacent to the ependymal lining or very small malformations, which either self-destroy because of the hemorrhage or do not opacify on angiography, may cause these cases. In some reports, patients whose angiographic findings were normal while they lived showed a vascular malformation at autopsy.13)22) PIVH is frequently caused by vascular malformations, including cavernous angiomas and aneurysms. Some researchers have suggested that malformations are more probable in young patients.13)22)

PIVH was attributed to hypertension in 9 of our patients. However, we prefer to speak in terms of association rather than causality, because we cannot prove that hypertension in fact caused the bleeding. Hypertension was the only identified risk factor in 50%-70% of patients in the series,1)11)13) and it was present in all patients reported by Gates et al.6)

In  literature review, the most frequent cause of PIVH was a very small, parenchymatous, hypertensive hemorrhage, originating in tissues very close to the ventricular system (caudate and thalamus), of a type that can go undetected by CT or arise in the choroid plexus. We therefore believe that hypertension can induce hemorrhage in choroidal arteries.

This study agrees with previous work regarding the high probability that thalamic ICH will rupture into the ventricles. This may be due to the thalamus? anatomic proximity to the third ventricle, as well as to blood's tendency to spread medially. Finally, one of our patients had a suspected intraventricular tumor, and previous studies have also reported such. A wide range of other possible causes of PIVH has been reported in the literature. Recently, CT, computed tomography angiography (CTA), magnetic resonance image (MRI), and magnetic resonance angiography (MRA) have come into use as noninvasive screening procedures for intracranial vascular abnormalities. Hence, these noninvasive imaging modalities are useful for screening for PIVH, particularly in older, hypertensive patients. MRI is useful for investigating possible vascular malformations, and MRA and CTA are likewise useful for aneurysm investigation. However, a negative result cannot completely exclude a vascular lesion, and a definitive diagnosis and treatment planning may require conventional cerebral angiography.22)23)

3.  Prognosis & Risk factors

Hydrocephalus is a frequent PIVH complication and is probably due to the obstruction of cerebrospinal fluid (CSF) circulation or impairment in meningeal absorption. Intuitively, it makes sense that IVH impacts clinical outcomes through several possible mechanisms.20) The ventricular system can provide an outlet for IVH expansion with perhaps less resistance than does brain parenchyma, and IVH volume can independently exert a mass effect on the surrounding brain tissue. In addition, obstruction of the cerebrospinal fluid can cause obstructive hydrocephalus, which can raise intracranial pressure, resulting in global impairment.7)12)19) Finally, the presence of blood in the CSF may represent a global injury to the brain, whereas the original IVH may only result in a focal deficit. It was not surprising that hematoma volume and degree of midline shift correlated positively with mortality. If the IVH was close to the foramen of Monro or within the third or fourth ventricles, the likelihood of obstructive hydrocephalus increased, which increased the chance of a lethal result. Acute hydrocephalus contributed significantly to death and deterioration in the acute stages. Brott et al.2) speculated that hemorrhages originating in the periventricular regions are more likely to expand toward the nearby ventricle because the fluid spaces are more compressible than the surrounding brain parenchyma is, as the CSF redistributes extracranially. The results of Young et al.21) support this. They found that thalamic hemorrhages, with their proximity to the ventricles, correlated with larger IVH volumes and worse outcomes8)10)19) and showed a close correlation between baseline intraventricular blood volume and outcome. Similarly, they found deep hemorrhages in association with increased incidence of obstructive hydrocephalus, which results in raised intracranial pressure, beyond the direct effects due to the hemorrhage volume. Prognosis would logically seem related to the amount of blood; the more severe the hemorrhage, the worse the prognosis, and our study shows possibility of this relationship. However, some authors have not found a lethal volume of intraventricular hematoma or a correlation between hematoma size and outcome.1)3)13)

The correlation between IVH and increased morbidity is not clearly understood. Certainly, the CSF outflow blockage with obstructive hydrocephalus and subsequent increase of intracranial pressure (and, therefore, the reduction in cerebral perfusion pressure) plays an important prognostic role.20) Hydrocephalus is an independent outcome predictor in spontaneous IVH. The observation that IVH volume may be associated with a commensurate decrease in global cerebral blood flow further supports this concept. Interestingly, in other studies, outcomes did not differ in those patients treated by ventriculostomy. This may support the hypothesis that the enhanced morbidity associated with IVH is due, at least in part, to the pressure the clot exerts on periventricular structures. This emphasizes the possible impact of any treatment that prevents IVH or limits further IVH expansion. Others have correlated total IVH volume with outcome via a ?ethal volume?of IVH, which is greater than 20 mL.8)21) Proposed mechanisms for this IVH-induced morbidity include development of hydrocephalus, decreased consciousness, and IVH-induced inflammation. The greater the age and the further the blood pressure is out of the normal range (whether higher or lower), the worse the prognosis.12) Research has also confirmed that clinical condition and level of consciousness on admission significantly influence prognosis.2)13) A good prognosis in such circumstances seems due to the absence of parenchymatous damage.13)

Some authors have noted memory difficulties, a common consequence in such patients.5)13)19) Some have suggested that these memory problems are due to a lesion of the fornix or dorsomedian thalamic nuclei. In addition, in patients whose initial clinical condition is not serious, early treatment strategies aimed to prevent increases in ventricular enlargement may improve their prognoses.

4.  Treatment

The appropriate treatment for PIVH is not clear, and the prognosis is variable, with mortality rates previously reported as 40-83%.1)9)13)19)20) The need of extraventricular drainage in IVH patients is seven times greater than in other types of hemorrhage; however, the poor outcome rate for EVD patients is alarmingly high.8)14)20) While this is likely due to the larger volume of IVH and hydrocephalus, EVD related morbidity such as rebleeding and infection may contribute to the observed poor outcome in these patients, although this has been recently debated. IVH patients' poor outcomes, with or without EVD, should encourage the development and testing of new treatments for IVH, such as intraventricular instillation of thrombolytic agents.4)15-18)

Clinicians have used for IVH due to a variety of causes, with good results and no bleeding complications, and, consequently, can make good use of it. However, establishing that it improves outcomes or reduces the need for ventriculoperitoneal shunting would be a complicated analysis, due to both IVH's variable causes and the many prognostic factors involved. Perhaps the aggressive management of hydrocephalus and the use of thrombolytic agents in the future will improve the outcomes of patients with primary intraventricular hemorrhage.

Conclusion

Although present technology allows us to reach a diagnosis of PIVH in many patients, its etiology and clinical manifestations are varied and remain largely unknown, due to rarity of such cases. Our study shows a possible relationship between hemorrhage volume and prognosis, with overall results and prognoses relatively better than for secondary IVH. However, evaluating and clarifying the nature of PIVH requires experience with more cases.

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