Pseudotumour Cerebri in a Patient with Acute Promyelocytic Leukemia on Treatment with All Transretinoic Acid- A Case Report

Abstract

Acute promyelocytic leukemia is a highly curable subtype of acute myeloid leukemia and 85% of these patients achieve long term survival with current therapy. We present the case report of a female patient with acute promyelocytic leukemia treated with arsenic trioxide and all transretinoic acid that subsequently developed abrupt onset lateral rectus palsy and decreased visual acuity due to pseudotumour cerebri. We treated the patient with repeated therapeutic lumbar punctures and acetazolamide, following which the lateral rectus palsy and vision improved.

Keywords: Acute promyelocytic leukemia; Pseudotumour cerebri; All trans retinoic acid

Introduction

Acute Promyelocytic Leukemia (APL, previously called AML-M3) is characterized by the balanced translocation t(15;17)(q24.1;q21.1). This rearrangement is seen in 13 percent of newly diagnosed AML and is highly specific for APL [1]. Without treatment, APL is the most malignant form of AML with a median survival of less than one month [2].

A key component of therapy is the use of ATRA, which promotes the terminal differentiation of malignant promyelocytes to mature neutrophils.

However, ATRA has also been associated with several side effects, including skin problems, reversible elevation in liver enzymes, abnormal lipid levels, hypothyroidism, and headaches. ATRA has also been associated with cerebral and myocardial infarction, corneal deposits secondary to hypercalcemia, scrotal ulcerations, Sweet’s syndrome, Fournier’s gangrene, acute promyelocytic leukemia differentiation syndrome, and pseudotumour cerebri.

Pseudotumour cerebri is characterized by symptoms and signs isolated to those produced by increased intracranial pressure (e.g., headache, papilledema, vision loss, cranial nerve palsies), with normal cerebrospinal fluid composition, and no other cause of intracranial hypertension evident on neuroimaging or other evaluations [3]. This complication is commonly seen in pediatrics age group and rare in adults. Usually occurs after long term use of ATRA, but here our patient developed it within the first 2 weeks of treatment. We describe the case report of a 32yr old female with acute promyelocytic leukemia treated with all transretinoic acid and arsenic trioxide, which developed left lateral rectus palsy and bilateral visual loss due to pseudotumour cerebri.

Case Report

We describe the case of a 32yr old female who presented with fever, dysuria of 4 days duration. There was no history of myalgia or arthralgia. No history of abdominal pain, loose stools. No history of cough or expectoration. No history of loss of weight or appetite. No history of bleeding manifestations. On examination there were no remarkable findings except for pallor. The Investigation were as follows: Hb was 7.2 g/dl, total count of 33 x 109/ L, platelet count of 44 x109/L. Renal and liver function tests were normal and coagulation profile was also normal. Considering the possibility of hematological malignancy a peripheral smear examination was done which revealed acute promyelocytic leukemia which was further confirmed with bone marrow study. A qualitative RT PCR for PML RARa was done, which was positive. Patient was started on induction therapy with arsenic trioxide 10mg IV and all transretinoic acid (45mg/ m2 in 2 divided doses). On day 7 after starting treatment, patient developed diplopia due to left lateral rectus palsy. Subsequently, developed progressive visual loss. No history of headache or vomiting. Neurological examination showed left lateral rectus palsy. Fundus examination showed bilateral papilloedema (Figure 1). No other focal neurological deficits. She was evaluated with CT head and MRI Brain which was both normal. MR Venogram was also done which ruled out sinus thrombosis. Suspecting a possibility of pseudotumour cerebri, we proceeded with CSF study which showed an opening pressure of 300 mm of water. The biochemical and cytological analysis of the CSF was normal. Following the lumbar puncture patient showed minimal improvement in diplopia and visual acuity. She was treated with acetazolamide and repeated therapeutic lumbar punctures following which she improved over the next 2 weeks. Dose modification of all Trans’ retinoic acid was not done since the patient improved.

    

    

    Figure 1:  Fundus photo showing papilloedema and hemorrhages.