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Year : 2015  |  Volume : 11  |  Issue : 4  |  Page : 1012-1014

A rare case of chemotherapy induced reversible cerebral vasoconstriction syndrome in a patient of acute lymphocytic leukemia

Department of Radiodiagnosis and Imaging, King Edward Memorial Hospital and Seth GS Medical College, Mumbai, Maharashtra, India

Date of Web Publication03-Nov-2015

Correspondence Address:
Namita Kamath
12/501, Millennium Park, Hari Om Nagar, Mulund East, Mumbai - 400 081, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.168993

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 > Abstract 

Neurotoxic reactions of chemotherapy occur frequently and are often dose limiting side effects of chemotherapy. It is important to differentiate these various nonneoplastic effects from metastases, or sometimes even from each other, since the therapeutic approach differs accordingly. To arrive at a definitive and comprehensive diagnosis, the radiologist should integrate imaging findings, clinical signs, and laboratory results together. Here we present a unique case of chemotherapy induced reversible cerebral vasoconstriction syndrome in a 13-year-old patient of acute lymphoblastic leukemia.

Keywords: Acute lymphoblastic leukemia, posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome

How to cite this article:
Sankhe S, Kamath N, Sahu A. A rare case of chemotherapy induced reversible cerebral vasoconstriction syndrome in a patient of acute lymphocytic leukemia. J Can Res Ther 2015;11:1012-4

How to cite this URL:
Sankhe S, Kamath N, Sahu A. A rare case of chemotherapy induced reversible cerebral vasoconstriction syndrome in a patient of acute lymphocytic leukemia. J Can Res Ther [serial online] 2015 [cited 2020 Jan 29];11:1012-4. Available from: http://www.cancerjournal.net/text.asp?2015/11/4/1012/168993

 > Introduction Top

Reversible cerebral vasoconstriction syndrome (RCVS), also known as benign central nervous system (CNS) arteriopathy, is one of a group of conditions which make up the RCVS, not to be confused with posterior reversible encephalopathy syndrome (PRES), although there is overlap both in the presumed underlying mechanisms and predisposing factors.

 > Case report Top

A 13-year-old boy presented to our magnetic resonance imaging (MRI) department with acute onset seizure activity in prior 24 h with three episodes of convulsions. The patient was a known case of acute lymphoblastic leukemia on intensive phase of chemotherapy consisting of daunorubicin, vincristine, and steroids which was started 4 days back. The child was mildly hypertensive. Basic blood investigations were within normal limits. CNS examination revealed altered mental status in the form of stupor in the postictal phase followed by normal mental status. The seizure activity was of generalized tonic-clonic type followed by a postictal stupor of 30 min. The child had normal sensorium in the interictal phase. Motor and sensory examinations were normal.

Initial MRI revealed subcortical T2-weighted and fluid attenuated inversion recovery hyperintensities in the parieto-occipital white matter. There was no postcontrast enhancement of these lesions [Figure 1]. All these findings were consistent with PRES.
Figure 1: Fluid attenuated inversion recovery image showing parieto-occipital subcortical white matter hyperintensities

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The child continued to have convulsions after every dose of chemotherapy. Hence, he was referred back to our department for follow-up imaging after 5 days of initial MRI. The repeat MRI showed an increase in the white matter lesion. There were patchy areas of restricted diffusion in the cortex and left hippocampus which were most likely postictal. We suspected a vascular cause as a reason behind the augmentation of the imaging findings. Hence, a time of flight magnetic resonance angiography was done. This revealed attenuation of the caliber of all the vessels of circle of Willis [Figure 2]. Hence, the diagnosis of RCVS was reached.
Figure 2: T2-weighted image increase in the white matter lesion. Time of flight magnetic resonance angiography revealed attenuation of the caliber of all the vessels of circle of Willis. Final follow-up imaging done 21 after the first scan shows resolution of all the white matter lesion and restitution of the caliber of the vessels in the circle of Willis

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All the chemotherapy drugs were stopped and follow-up imaging done 10 days after first imaging showed resolution of the white matter lesion and opening up of the caliber of the vessels.

Further follow-up imaging done 21 days after first imaging showed complete resolution of all the lesions and restitution of the normal caliber of the intracranial vessels [Figure 2].

 > Discussion Top

Neurotoxic side effects of chemotherapy occur commonly and are often a rationale to limit the dose of chemotherapy. Since bone marrow toxicity, as the major limiting factor in most chemotherapeutic regimens, can be overcome with growth factors or bone marrow transplantation, the use of higher doses of chemotherapy is possible, which increases the risk of neurotoxicity. Central neurotoxicity ranges from such as cognitive deficits, seizures, cerebellar dysfunction, psychiatric symptoms, and extrapyramidal disorders. [1],[2]

The development of these harmful effects may have an acute, subacute, or delayed course, and may be reversible or (partially) irreversible. [1],[3],[4] The incidence of central neurotoxicity of chemotherapy depends on the chemotherapeutic drug used, the frequency of administration, the dosage prescribed, the route of administration, and concomitant cranial irradiation. [1],[2],[5],[6],[7]

There are three basic categories under the heading of nonneoplastic CNS manifestations: (1) Direct toxicity of therapeutic agents; (2) radiation effects of the radiotherapy given primarily not to the brain, but to tumors located adjacent to the brain; and (3) remote effects of the primary tumor (so-called paraneoplastic syndromes). Direct toxicity includes white matter disease, the PRES, and vascular effects resulting in either venous/arterial thrombosis or hemorrhage. [8],[9],[10]

RCVS (sometimes called Call-Fleming syndrome) is a poorly understood disease in which the arteries of the brain develop vasospasm without a clear cause (such as hemorrhage or trauma). RCVS can occur spontaneously or be secondary to a precipitating factor. The pathogenesis of RCVS remains poorly understood. Current consensus on the etiology focuses around alteration of cerebral vascular tone. There appears to be an interaction between sympathetic over activity and endothelial dysfunction, resulting in dysautoregulation.

Up to two-thirds of RCVS cases are associated with an underlying condition or exposure, particularly vasoactive or recreational drug use, complications of pregnancy (eclampsia and preeclampsia), and the adjustment period following childbirth called puerperium. Vasoactive drug use is found in about 50% of cases. Implicated drugs include selective serotonin reuptake inhibitors, alpha-sympathomimetic decongestants, acute migraine medications, pseudoephedrine, epinephrine, cocaine, and cannabis, among many others. RCVS is a less documented side effect of chemotherapeutic drugs. Cyclophosphamide and immunosuppressive drugs like have been implicated as causative agents of secondary RCVS. Although the exact cause was not known in our case, stoppage of the chemotherapeutic drugs lead to reversal of the imaging finding lead us to believe that maybe one or all of the drugs could be the offending agent.

PRES is a known complication of RCVS. The exact mechanism by which this condition is caused is not known though there have been two postulated theories, the cytotoxic theory and the vasogenic theory. According to the cytotoxic theory, a direct toxic effect on the endothelial cells of the cerebral vasculature results in cell autonomous dysfunction. Whereas, according to the vasogenic theory, an acute increase in blood pressure overrides the autoregulation of cerebral mean arterial pressure, leading to vasodilatation and autonomous endothelial insult. The end result via both pathways is the diffusion of plasma proteins and cells into the extracellular space and subsequent cerebral edema.

It is imperative to distinguish between PRES and RCVS. Withdrawal of the offending agent and control of blood pressure are pivotal to reverse the fatal consequences and is enough to treat PRES. Nimodipine and other calcium channel blockers are required as a supportive treatment for RCVS.

Hypertension is a frequent feature in cases of PRES and patients can improve dramatically with lowering of blood pressure. Most seizures respond well to antiepileptic drugs, and the drug can be tapered off quickly with reversal of neurological symptoms and imaging findings.

RCVS should be considered as a differential in patients who showing progression of lesion in the subsequent scan in a suspected case of PRES. The prognosis of RCVS is good and symptoms are reversible if the diagnosis is made promptly and remedial measures are taken.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

Verstappen CC, Heimans JJ, Hoekman K, Postma TJ. Neurotoxic complications of chemotherapy in patients with cancer: Clinical signs and optimal management. Drugs 2003;63:1549-63.  Back to cited text no. 1
Dietrich J, Monje M, Wefel J, Meyers C. Clinical patterns and biological correlates of cognitive dysfunction associated with cancer therapy. Oncologist 2008;13:1285-95.  Back to cited text no. 2
Ahles TA, Saykin AJ, Furstenberg CT, Cole B, Mott LA, Skalla K, et al. Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma. J Clin Oncol 2002;20:485-93.  Back to cited text no. 3
Schagen SB, Muller MJ, Boogerd W, Rosenbrand RM, van Rhijn D, Rodenhuis S, et al. Late effects of adjuvant chemotherapy on cognitive function: A follow-up study in breast cancer patients. Ann Oncol 2002;13:1387-97.  Back to cited text no. 4
Boogerd W, van den Bent MJ, Koehler PJ, Heimans JJ, van der Sande JJ, Aaronson NK, et al. The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: A randomised study. Eur J Cancer 2004;40:2726-33.  Back to cited text no. 5
van Dam FS, Schagen SB, Muller MJ, Boogerd W, vd Wall E, Droogleever Fortuyn ME, et al. Impairment of cognitive function in women receiving adjuvant treatment for high-risk breast cancer: High-dose versus standard-dose chemotherapy. J Natl Cancer Inst 1998;90:210-8.  Back to cited text no. 6
Schagen SB, Muller MJ, Boogerd W, Mellenbergh GJ, van Dam FS. Change in cognitive function after chemotherapy: A prospective longitudinal study in breast cancer patients. J Natl Cancer Inst 2006;98:1742-5.  Back to cited text no. 7
Vázquez E, Lucaya J, Castellote A, Piqueras J, Sainz P, Olivé T, et al. Neuroimaging in pediatric leukemia and lymphoma: Differential diagnosis. Radiographics 2002;22:1411-28.  Back to cited text no. 8
Dietrich J, Marienhagen J, Schalke B, Bogdahn U, Schlachetzki F. Vascular neurotoxicity following chemotherapy with cisplatin, ifosfamide, and etoposide. Ann Pharmacother 2004;38:242-6.  Back to cited text no. 9
Tam CS, Galanos J, Seymour JF, Pitman AG, Stark RJ, Prince HM. Reversible posterior leukoencephalopathy syndrome complicating cytotoxic chemotherapy for hematologic malignancies. Am J Hematol 2004;77:72-6.  Back to cited text no. 10


  [Figure 1], [Figure 2]


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