Intraventricular hemorrhage (IVH) is a significant and independent contributor to morbidity, with an estimated 30-day mortality rate of 40%–80%¹⁵⁾. In hemorrhagic moyamoya disease (MMD), 30%–40% of cases are primary IVH, and IVH is more frequently associated with intracerebral hemorrhage (ICH) than primary ICH^4,9,11,15). With IVH, external ventricular drains (EVD) are often necessary for cerebrospinal fluid (CSF) diversion to reduce intracranial pressure (ICP).

Intraventricular recombinant tissue plasminogen activator (rt-PA) can be considered to reduce IVH burden and further reduce ICP. The safety of intraventricular rt-PA use was shown in the CLEAR III trial¹⁵⁾; however, patients with increased risk of ICH were excluded, including those with MMD, suspected or untreated ruptured cerebral aneurysm, ruptured intracranial arteriovenous malformation (AVM), choroid plexus malformation, or clotting disorders. Thus, the safety of intraventricular rt-PA use in patients with MMD is unknown. Herein, we introduce a case where intraventricular rt-PA was used for rescue therapy to reduce ICP in a patient with ICH with IVH who had underlying MMD.

A 39-year-old female was admitted with a generalized tonic-clonic seizure lasting about 3 min and subsequent altered mentality. She had a history of Grave’s disease and right posterior cerebral artery territory infarction and was diagnosed with Suzuki stage III MMD 7 years before admission; at that time, bypass surgery was recommended but declined, and the patient was lost to follow-up. She was taking 10 mg of methimazole daily but no antithrombotic agents at admission. The initial neurological exam showed a Glasgow Coma Scale of E2V3M5 with motor grade III/III for the upper extremities and III/IV for the lower extremities. Computed tomography (CT) scan revealed a left posterior thalamic ICH and diffuse IVH extending from both lateral ventricles to the 3rd and 4th ventricles with acute hydrocephalus (Fig. 1). The modified Graeb score was 24. Bilateral EVDs were placed, and she was admitted to the neurological intensive care unit. For controlling ICP, deep sedation with RASS -4 was achieved using dexmedetomidine, remifentanil, and propofol, with targeted normothermia (37.5°C) temperature management. The right EVD became nonfunctional immediately after surgery, presumably due to obstruction of the catheter tip by IVH. Hypertonic saline was administered every 6 hours, and cerebral perfusion pressure > 80 mmHg was maintained.

The next day, ICP increased to 24 mmHg, and the left EVD intermittently failed to show oscillation, and a follow-up brain CT revealed no change in IVH volume. Given that both lateral ventricles were filled with hematoma and EVD revision alone was unlikely to restore adequate CSF drainage, we concluded that intraventricular rt-PA injection represented the most reasonable therapeutic option. The patient’s family was thoroughly informed of the potential risks, including rebleeding and death, and provided informed consent for the off-label use of intraventricular rt-PA. As the ICH was located on the left and suspected to be the primary bleeding focus, rt-PA was administered via the right EVD to minimize the risk of rebleeding.

Intraventricular thrombolysis was performed using a modified rt-PA protocol based on the CLEAR III trial¹⁵⁾. One mL of rt-PA was administered via the right EVD, followed by a 2 mL flush of normal saline. The right EVD was then clamped for 1 hour before being declamped. Immediately after declamping, ICP decreased to 4 mmHg before stabilizing (Fig. 2).

CT the next day showed improvement in hydrocephalus and recanalization of the right foramen of Monro as well as the 3rd and 4th ventricles. On postoperative day (POD) 7, IVH was resolved; there was no hydrocephalus, and the left EVD was removed. The right EVD was removed on POD 17 (Fig. 1). On POD 20, cerebral angiography revealed a pseudoaneurysm at the left distal anterior choroidal artery, which was likely the cause of this event (Fig. 3). The patient was discharged to a rehabilitation facility and had left encephaloduroarteriosynangiosis (EDAS) surgery 2 months later. The patient remained under outpatient follow-up without specific complications and underwent right EDAS surgery 11 months after the initial diagnosis.

This case describes a patient who presented with IVH secondary to MMD. Although bilateral EVDs were placed, the right EVD became occluded immediately due to a large hematoma, and the left EVD became partially obstructed, allowing only intermittent ICP monitoring. While the safety of intraventricular rt-PA in patients with MMD has not been established, we decided that reducing the hematoma burden was essential for controlling ICP. Therefore, a single dose of intraventricular rt-PA was administered as a rescue therapy via the right ventricle, opposite to the left side suspected as the primary source of bleeding. Following the injection, EVD patency was restored, ICP was stabilized, and the patient was managed successfully without complications.

MMD, which predominantly affects East Asian populations, is characterized by progressive stenosis or occlusion of the terminal intracranial carotid arteries and the subsequent development of fragile compensatory collateral vessels²⁾. ICH in MMD often results from the rupture of these vessels, which are prone to elevated hemodynamic stress as well as microaneurysms or pseudoaneurysms as the disease progresses¹⁾. In response to chronic cerebral hypoperfusion, patients with MMD often exhibit compensatory vasodilation, leading to increased cerebral blood volume and altered cerebrovascular reactivity⁴⁾. This disturbed hemodynamic state may predispose patients to secondary brain injury after acute neurological insult due to impaired autoregulation and reduced capacity to buffer ICP fluctuations. For this reason, patients with MMD may be particularly vulnerable to ICP crises. Moreover, approximately 30% of patients with MMD present with ICH due to rupture of fragile collateral vessels harboring microaneurysms or pseudoaneurysms²⁾. These findings underscore the need for further research on the use of rt-PA to control ICP.

Given the unique vascular pathology of MMD, a standardized protocol such as that used in the CLEAR III trial¹⁵⁾—which employed an 8-h interval for intraventricular rt-PA administration—may not be appropriate for MMD. Instead, a modified treatment approach incorporating individualized risk-benefit assessments may be necessary to optimize safety and efficacy. Further studies are warranted to establish evidence-based guidelines for the use of rt-PA in patients with MMD, particularly for elevated ICP.

The optimal approach to EVD placement, whether unilateral or bilateral, in patients with IVH remains a topic of debate. Although bilateral EVDs carry a higher risk of infection than unilateral drainage¹⁴⁾, they may be necessary in cases of severe IVH or hydrocephalus to ensure effective CSF diversion and hematoma clearance. Studies have shown that bilateral EVDs can improve hematoma resolution and ICP control compared to unilateral placement¹³⁾. In our case, the patient presented with massive IVH, acute hydrocephalus, and seizure, suggesting markedly elevated ICP at baseline. Bilateral EVDs placement was considered the most appropriate strategy for prompt ICP reduction.

Several case reports have demonstrated the potential feasibility of intraventricular fibrinolysis, despite the limited evidence supporting it in patients at high risk of ICH (Table 1).

Rahmani et al. reported a patient with IVH secondary to MMD and no aneurysm on cerebral angiography¹⁰⁾. Intraventricular rt-PA was administered in eight doses, resulting in significant clot resolution and EVD weaning two days after the final dose. In this case, the absence of a ruptured aneurysm likely permitted a more liberal dosing strategy.

Shen et al. described an MMD-associated IVH case treated with bilateral EVDs¹²⁾. Continuous irrigation using lactated Ringer’s solution was initiated via one ventricle and drained contralaterally. As clot reduction remained suboptimal after two days, they administered urokinase (72,000 IU/day in 1,500 mL of lactated Ringer’s) for five days. Ventricular clearance was achieved within four days of urokinase use. No bleeding occurred, but the patient developed meningitis, which resolved with antibiotics.

In contrast to these cases, we administered a single dose of rt-PA as a rescue therapy due to the presence of an aneurysm. Although hematoma resolution was more gradual, EVD patency was restored and maintained without hemorrhagic or infectious complications.

Aside from MMD-related IVH, over ten cases have been reported where intraventricular fibrinolysis was used in patients with ruptured AVM^1,3,5). In some of these, fibrinolysis was used as a rescue strategy for uncontrolled ICP, while others adopted a more proactive approach. These cases further underscore the potential utility of intraventricular fibrinolysis in complex hemorrhagic conditions.

Nonetheless, most reports remain anecdotal, and protocols regarding dose, agent selection, and timing remain unstandardized. The risk of publication bias should also be considered.

This case highlights the challenges of using rt-PA for ICP control in MMD due to its unique vascular pathology and increased hemorrhagic risk. Further research is needed to develop tailored guidelines for rt-PA use in MMD.