Severe Cerebral Vasospasm and Childhood Arterial Ischemic Stroke After Intrathecal Cytarabine

Abstract

We report on 2 patients who developed widespread cerebral vasospasm and arterial ischemic strokes (AIS) after application of intrathecal (IT) cytarabine. In a 3-year-old child with acute lymphoblastic leukemia (ALL), left leg weakness, hyperreflexia, and clonus were noted 4 days after her first dose of IT cytarabine during the induction phase of her chemotherapy. Cerebral MRI revealed multiple acute cerebral ischemic infarcts and widespread cerebral vasospasm. A 5-year-old girl complained of right arm and leg pain and began limping 11 days after IT cytarabine. Symptoms progressed to right dense hemiplegia, left gaze deviation, headache, and speech arrest. MRI revealed 2 large cortical areas of diffusion restriction in the right frontal and left parietal lobes. Cerebral magnetic resonance angiography (MRA) showed irregular narrowing affecting much of the intracranial arterial circulation. Although the first child fully recovered from her neurologic symptoms, the second patient had persistent hemiplegia on follow-up. Including this report, there are now 4 pediatric ALL cases of severe cerebral vasospasm and AIS in the context of IT cytarabine administration, strongly suggesting a true association. Differential diagnosis and management issues are discussed. Along with the more widespread use of MRI and MRA, the true frequency of this severe adverse effect will become clearer in future. For any child with neurologic symptoms within hours or days of receiving IT cytarabine, a low threshold for cerebral imaging with MRI and MRA is recommended.

Cerebral Vasospasm after Open Fenestration of an Arachnoid Cyst in a 4-Year-Old Boy: Case Report and Review of the Literature

“…Pediatric cases of nonaneurysmal, non-TBI vasospasm have been reported following open tumor resection [13-16] and administration of certain chemotherapies [17, 18] (Table 1). These patients presented between POD5 and POD12.…”

“…Outcomes ranged from severe disability to full recovery. All authors encourage prompt diagnosis and treatment, as the high morbidity and mortality reported may be in part related to a delay in diagnosis [18, 19]. …”

Definitive Diagnostic Evaluation of the Child With Arterial Ischemic Stroke and Approaches to Secondary Stroke Prevention

“…Generally, inflammatory arteriopathies such as focal cerebral arteriopathy, inflammatory subtype (FCA i ) and primary angiitis of the central nervous system (PACNS) demonstrate circumferential enhancement of the vessel wall with periadventitial involvement, whereas noninflammatory arteriopathies such as reversible cerebral vasoconstriction syndrome more often show little to no enhancement. 9,11,12 Reported VWI findings in dissection include eccentric mural enhancement related to inflammation, and variable T1 hyperintensity related to intramural hematoma. 13 Evolution of signal intensity within the intramural hematoma over time has been described in patients with extracranial arterial dissections, with highest lesion conspicuity occurring in the late subacute period 7 to 14 days after lesion initiation.…”

Reversible cerebral vasoconstriction syndrome after intrathecal cytarabine

“… 1 Less commonly, the use of chemotherapeutic agents can precipitate RCVS and intrathecal cytarabine has been reported as a rare causative agent in the pediatric population. 2 , 3 , 4 , 5 , 6 …”