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Abstract Details

Rare Case of Diffuse Cerebral Microhemorrhages from Methotrexate Toxicity in Patient with Acute Lymphoblastic Leukemia
Cerebrovascular Disease and Interventional Neurology
P10 - Poster Session 10 (5:30 PM-6:30 PM)
4-013
  NA
20-year-old right-handed man with very-high-risk pre-B-cell acute lymphoblastic leukemia CNS1 post-induction and consolidation per ALL113 protocol, on high-dose intrathecal and intravenous methotrexate maintenance therapy, interrupted due to toxicity, pancytopenia, infection and deconditioning. During consolidation therapy, the patient developed new-onset seizures. Initial MRI brain at time of first seizure showed a small number of microhemorrhages (~3) on susceptibility weighted imaging. Several months later, neurology was consulted due to new imaging findings in the setting of a breakthrough seizure.
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Following most recent seizure-like activity, non-contrast CT head revealed two foci of intraparenchymal hemorrhage. MRI brain SWI additionally revealed interval development of diffuse microhemorrhages (>100 bilaterally). Per neuroradiological interpretation, this may be seen in the setting of ALL with hyperviscosity syndrome, necrotizing vasculopathy, methotrexate toxicity as well as with disseminated intravascular coagulation. This was 6 months after induction therapy and 1.5 months from last dose of methotrexate.

Patient denied having a headache prior to or during his presentation. Head trauma was ruled out from history. Neurological examination was significant for generalized weakness (4- to 4+/5 throughout), except 1/5 bilateral dorsiflexion weakness with full strength on plantar flexion.

 No clinical or laboratory evidence of DIC, recent trauma, hyperviscosity syndrome or vasculitis/vasculopathy.    

 
Neurotoxicity is reported in 1%-4.5% of patients receiving high-dose methotrexate therapy, ranging from leukoencephalopathy to stroke-like phenomena. Limited number of cases of intracerebral hemorrhages have been reported with methotrexate therapy, however diffuse cerebral microhemorrhages have never been previously described. Cerebral microhemorrhages have been reported in patients with ALL who underwent cranial radiation therapy, however our patient did not. The development of diffuse microhemorrhages is likely multifactorial in this case. We hypothesize that the pathogenesis is methotrexate neurotoxicity exacerbated by increased blood-brain barrier leakage from seizure activity, in the setting of thrombocytopenia and coagulopathy, leading to the perfect storm.
Authors/Disclosures
Veronika Solnicky, MD (University of Maryland)
PRESENTER 		No disclosure on file
Chelsea S. Kidwell, MD (University of Arizona Department of Neurology) No disclosure on file