Progressive multifocal leukoencephalopathy (PML) in a patient without known immunodeficiency: a case report

Abstract

Case Presentation: Patient D.M.C.S., female, 68 years old, nursing technician, smoker currently abstinent (10.5 pack-years), former social alcohol user, without known comorbidities, initiated asthenia, apathy, and affective symptoms. After two months, she developed visual and olfactory hallucinations, and one month later, she presented with motor aphasia and left hemiplegia. Initial brain MRI revealed multifocal demyelinating lesions with T2/FLAIR hyperintensity, diffusion restriction, and mild contrast enhancement, suggestive of progressive multifocal leukoencephalopathy (PML). She developed progressive neurological deterioration requiring multiple hospitalizations, with dysphagia and bronchoaspiration. Follow-up imaging showed lesion progression with supra- and infratentorial involvement, including brainstem, basal ganglia, and corticospinal tract, without significant mass effect, consistent with an infectious demyelinating process. Initial CSF showed mild pleocytosis and hypoglycorrhachia; repeat analysis revealed a lymphocytic pattern, elevated protein, and normal glucose. Type 2 oligoclonal bands indicated intrathecal IgG synthesis. JC virus PCR in CSF, performed approximately three months after symptom onset, was positive, confirming PML and establishing a definitive diagnosis in the appropriate clinical-radiological context. Brain biopsy was inconclusive. Primary CNS lymphoma and inflammatory vasculopathy were considered but excluded based on clinical-radiological evolution. Extensive infectious, autoimmune, and neoplastic workup was negative. Serologies for HIV, HTLV, hepatitis viruses, and VDRL were non-reactive. Serum immunoglobulins were normal (IgA 371, IgM 79, IgG 1799). Complete blood count showed no significant lymphopenia. CT scans showed no evidence of malignancy. Despite empirical treatment, the patient developed decreased level of consciousness, aspiration pneumonia, and progressive functional decline. Eight months after symptom onset, given the poor prognosis, palliative care was initiated, and the patient died. Discussion: This case characterizes PML in a patient without known immunodeficiency. There was no history of immunosuppressive therapy, recurrent infections, or relevant systemic diseases. Evaluation did not reveal immunodeficiency, including negative serologies, normal immunoglobulin levels, absence of significant lymphopenia, and negative oncologic screening. Final Comments: This report reinforces the possibility of PML in apparently immunocompetent individuals, potentially related to immunosenescence and smoking, even at low to moderate exposure. It highlights the importance of including PML in the differential diagnosis of progressive leukoencephalopathies outside classical contexts and underscores the central role of JC virus detection in CSF. Additionally, PML may represent the initial manifestation of unrecognized immunosuppressive states, requiring systematic investigation and follow-up.