A 64-year-old Caucasian male with a past medical history of non-small cell lung cancer (NSCLC) (status post radiation therapy 5 years prior), chronic obstructive pulmonary disease, pulmonary embolism on rivaroxaban presented to the emergency department with worsening bilateral visual loss in the left field of vision for 4 weeks. On prior outpatient evaluation, there was initial concern for glaucoma but later there was suspicion of a central nervous system pathology prompting his arrival to the emergency department for further evaluation. He reported unintentional 30-pound weight loss over 2 months along with a progressive decline in short-term memory. He also reported recent falls due to subjective lower extremity weakness. He denied numbness, tingling, difficulty swallowing, slurred speech, difficulty finding words, headache, sleep disturbances, dizziness, nausea, vomiting, and bowel or bladder dysfunction. Vital signs were within the normal range. Physical examination was pertinent for left homonymous hemianopsia.
Initial laboratory workup including total blood count, electrolytes, lipid panel, TSH, HbA1C, ESR, vitamin B12, and folic acid was within normal range. C-reactive protein was mildly elevated 1.45 m/dl. MRI brain showed extensive, multifocal white matter signal abnormalities with subcortical U-Fiber involvement and sparing of adjacent gray matter with white matter lesions in the right hemisphere that were T2 hyperintense, T1 hypointense which did not enhance with gadolinium administration (Fig. 1). The imaging findings were strongly suggestive of PML, but differential diagnosis included viral encephalitis and acute disseminated encephalomyelitis.
The patient tested positive for Human Immunodeficiency Virus (HIV) using the 4th generation screening assay. HIV-1 viral load was 267,501 copies/ml, absolute cluster of differentiation 4 (CD4) cell count was 58/mm3 with CD4% 4%. Serology was positive with plasma JCV PCR showing < 500 copies/ ml. The autoimmune encephalitis panel was negative. Other infectious workups for syphilis, tuberculosis, gonorrhea, chlamydia, toxoplasmosis, cytomegalovirus and hepatitis were negative. Further inquiry revealed that the patient had a needle stick injury during his work in a laboratory many years ago. Antiretroviral therapy with once-daily fixed-dose Abacavir-Dolutegravir-Lamivudine was initiated along with trimethoprim-sulfamethoxazole regimen for Pneumocystis jerovecii prophylaxis. He was discharged home and lumbar puncture was performed as an outpatient. CSF analysis was positive for JCV on qualitative PCR. A definite diagnosis of PML was made at this time based on the overall clinical picture.
Two months after initial admission, the patient was re-admitted for left-sided weakness, declining functional status, repeated falls, and worsening vision loss. The patient's presentation was consistent with the progression of PML supported by the progression of white matter lesions on repeat brain MRI [Fig. 2]. There was no contrast enhancement thus immune reconstitution inflammatory syndrome (IRIS) was considered less likely. Repeat Lumbar puncture showed CSF normal protein and glucose levels, 5 nucleated WBC, 119 RBCs. CSF VDRL, HSV - 1 and - 2 PCR, cryptococcus antigen testing were negative. Serum fungal antibodies for Histoplasma, Blastomyces, Aspergillus, and Toxoplasmosis were negative. CD4 cell count had improved from the prior 58-144/mm3 from the time of HIV diagnosis. Intravenous (IV) Pembrolizumab 2 g/kg was started for compassionate use with plans to repeat every 4 weeks. Even after a week, there was no improvement in left hemiparesis and patient developed left hemineglect. He also developed hospital acquired pneumonia for which was treated with piperacillin-tazobactam. Due to deteriorating neurological status, a repeated brain MRI was performed which showed further progression of PML (Fig. 3). There was now localized mass effect and edema which were concerning for PML-IRIS. Dexamethasone 8 mg every 6 h was started with only a slight improvement in left-sided strength. The patient developed Clostridioides difficile colitis and oral vancomycin was initiated. Eventually, the patient was transitioned to hospice care and passed away.