SC13
Death Caused By Disseminated PML in a Natalizumab Treated MS Patient Whose Immune Competence Could Not be Restored
PML occurs in MS patients treated with Natalizumab. Medication cessation and treatment with plasmapheresis often provoke a brisk inflammatory reaction, the Immune Reconstitution Inflammatory Syndrome (IRIS).
Objectives:
We present a case of Natalizumab induced PML in an MS patient whose immune competence was not restored resulting in widespread infection ultimately causing death.
Methods:
Case report
Results:
The patient was 70 year old right handed woman with a 37 year history of MS. She had multiple mild exacerbations from 1999 to 2007 while treated with Glatiramer Acetate. Natalizumab was initiated in 2007 and produced radiologic and clinical stability. In 2010, after 36 infusions, she was found to be JC antibody positive and Natalizumab was discontinued. She worsened and Natalizumab was resumed after missing 3 doses.
In January 2013, after an additional 31 doses, she complained of subtle word finding difficulty. A MRI was reported unchanged, consistent with MS. Cerebrospinal fluid (CSF) PCR was positive for the JC virus. There was no history of prior immuno-suppressive treatment.
Five weeks after the last Natalizumab treatment she was admitted to Winthrop University Hospital and had 5 plasmapheresis treatments, followed by a 5 day course of IV Solu-Medrol 1 gm daily. There was no change in her MRI which was interpreted as consistent with MS and not indicative of PML, no enhancement was present.
10 days later her condition deteriorated with 4/5 right hemiparesis and difficulty following complex commands. A 3 day course of IV Solu-Medrol 1 gm daily was administered without benefit.
Follow up MRIs showed an expanding left hemisphere lesion that reached a size of 5cm x 5.9cm x 2.8 cm. It crossed the corpus callosum and involved the right hemisphere. There was no mass effect or enhancement. Mefloquine HCL and Mirtazapine were initiated.
Over the next 5 weeks she became globally aphasic with scant movement of her right hemibody. The family elected supportive care; she died 2 months after discharge. MRI performed 3 weeks prior to death showed no evidence of IRIS.
Conclusions:
This case is notable because of the inability to restore immune competence and the difficulty of diagnosing early PML by MRI. Three good quality MRIs were interpreted by 4 neuro-radiologists as consistent with MS, there was no radiologic suspicion of PML despite it being present in an early stage.
The initial PML presentation, subtle cognitive dysfunction without focal findings, made diagnosis difficult in an older patient with chronic psychiatric difficulties.
We speculate that initiating steroids before enhancement was noted on the MRI, and the patients older age, may have prevented the restoration of immune competence and allowed the virus to disseminate widely ultimately causing death.
On the basis of this case, we suggest that steroids not be initiated in older PML patients until there is radiologic evidence of early IRIS.