Progressive Multifocal Leukoencephalopathy in the Absence of Typical Radiological Changes: Can We Make a Diagnosis?

Patient: Female, 32 Final Diagnosis: Progressive multifocal leukoencephalopathy Symptoms: Progressive behavioral changes • seizures Medication: — Clinical Procedure: Management Specialty: Neurology OBJECTIVE: Rare disease BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a serious opportunistic infectious disease with high morbidity and mortality. Its incidence in multiple sclerosis (MS) patients has risen since the introduction of disease modifying drugs. In the absence of a specific treatment, the outcome depends heavily on early diagnosis, which illustrates the importance of the role of characteristic brain magnetic resonance imaging (MRI). However, when relying mainly on MRI, the diagnosis of cases with atypical radiological changes may be missed or delayed. CASE REPORT: A 32-year-old female diagnosed with elapsing remitting MS in 2009 was started on interferon-beta-1b that was escalated to natalizumab due to progression of the disease. Later, she was shifted to fingolimod as testing for John Cunningham polyoma virus (JCV) antibodies was positive. Three years later, she presented with a 3-week history of progressive walking impairment associated with twitching of her facial muscles and abnormal sensation all over her body that was associated with left hemi-paresis and sensory changes, in addition to truncal ataxia, which was treated with steroids as a relapse of MS. However, the patient continued to deteriorate and developed significant cognitive and behavioral changes. In view of this clinical picture, the diagnosis of PML was raised in spite of her atypical brain MRI features. Treatment with fingolimod was stopped and a sample of her cerebrospinal fluid was sent for JCV DNA analysis, which came back positive at 11 copies/mL. Treatment with mirtazepine and mefloquine was started, but the patient deteriorated further, and MRI showed severe changes consistent with immune reconstitution inflammatory syndrome. Intravenous steroids and intravenous immunoglobulin were given, and within a few weeks, the patient was stabilized and started to gradually improve. CONCLUSIONS: In patients at risk for developing PML who present with typical clinical features, testing for JCV DNA is recommended even in the absence of typical radiological findings in order to prevent any delay in the diagnosis.