IntroductionLeptomeningeal disease (LMD) occurs when tumor cells access the cerebrospinal fluid (CSF) pathways, travel to distant sites, settle and grow. The diagnosis depends upon clinical presentation, with confirmation through neuroimaging or CSF cytology. Findings consistent with LMD include contrast enhancement of the leptomeninges, subependyma, cranial and spinal nerves, and communicating hydrocephalus. Unfortunately, cytology-the diagnostic gold standard-may be negative even when disease is present. Recently, symptomatic LMD was reported in 8% of glioma patients, none of whom had positive cytology [1]. Increased LMD incidence may result from longer survivals and neuroimaging improvements. In gliomatous LMD, no established chemotherapy regimen exists, although general treatment guidelines include intrathecal chemotherapy with methotrexate, thiotepa and cytarabine. Temozolomide (TMZ) is an alkylating agent with good brain penetration and low toxicity, with a CSF:plasma drug ratio of 0.20 [2]. It is the standard of care in parenchymal gliomas, but little published experience exists for LMD.We report two anaplastic glioma patients enjoying durable responses of LMD to Temozolomide. Case studies Patient #1A 70 year old man presented with seizures. Brain magnetic resonance (MR) imaging revealed non-enhancing left frontotemporal tumor. Needle biopsy showed WHO Grade III (anaplastic) fibrillary astrocytoma. He received chemoradiation therapy, followed by TMZ chemotherapy, as published [3]. After three TMZ cycles, neuroimaging demonstrated increased enhancement. Surgical resection revealed mainly acellular material with small islands of preserved, viable tumor. Combination therapy with Temozolomide and Irinotecan was started. Neuroimaging progressively improved. Combination chemotherapy treatment was discontinued after six cycles for radiographic stability and fatigue. He completed nine total cycles of Temozolomide-containing regimens (Fig. 1) Clinical follow-up and surveillance imaging continued every 2 months. Eight months after chemotherapy cessation, multiple small enhancing foci within the temporal lobe-distant from the original resection cavity-suggested progressive disease. The postoperative cavity remained tumor free. He declined chemotherapy rechallenge. Two months later, urinary incontinence and gait disturbance occurred. Imaging revealed new linear lateral ventricle ependymal enhancement. Symptoms resolved following ventriculoperitoneal shunt placement. Three ventricular CSF cytology specimens were negative for malignant cells. Temozolomide rechallenge (200 mg/m 2 /day 9 5 days, on 28 day cycle) produced resolution of ependymal Sirisha Nandipati contributed equally to the manuscript.

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