Progressive multifocal leukoencephalopathy (sarcoidosis associated PML)
Presentation
1-2 week history of word finding difficulty, confusion, pins and needle sensation in right leg. No motor deficit, no headache. On high dose steroids for active pulmonary sarcoidosis (confirmed on EBUS node sampling), recently started azathioprine therapy.
Patient Data
Patchy right cerebral white matter hypoattenuation, up to but no involving cortex at many points. Not typical MCA or borderzone ischaemic territory. No established infarct, haematoma or mass. Netural mas
As identified on CT there is patchy confluent subcortical white matter change, asymmetric and predominantly right sided, with juxtacortical / U-fibre involvement. Mass neutral. Punctate "Milky Way" appearance on T2w imaging. Leading edge diffusion restriction. No abnormal enhancement.
The radiological appearances were considered most compatible with progressive multifocal leukoencephalopathy (PML). This is typified by the confluent asymmetric white matter abnormalities, with U-fibre involvement. Neurosarcoidosis remained in the differential, particularly given the known extra-CNS disease, but there was no enhancement or meningeal involvement evident.
Multiple CSF results were returned negative for John Cunningham virus (JC virus).
There was a clinical deterioration predominantly affecting speech fluency and processing (ACE 64/100).
One month later
Mild progression of white matter disease on interval MRIs. This study was performed prior to diagnostic brain biopsy. Ongoing confluent change, more extensive on the right, with leading edge diffusion restriction and no abnormal enhancement.
Post-brain biopsy FDG PET, performed to assess extra-CNS sarcoidosis.
Moderate uptake in bilateral upper lobe pulmonary, right hilar and subcarinal sites of active nodal disease.
Brain imaging demonstrating hypometabolism in the regions with confluent white matter change on MRI.
Despite multiple negative CSF samples, brain biopsy was positive for PML.
Microscopy: cores of neural tissue with mixed parenchymal infiltrate composed of large pleomorphic astrocytes, enlarged oligodendroglial nuclei with glassy violaceous nuclear inclusions, and numerous small CD3 positive lymphocytes, concentrated around blood vessels and macrophages. Foci of pallor consistent with demyelination. No significant CD20 B-cell component. SV40 staining demonstrates scattered JCV infected cells.
Tissue PCR JC virus level of 235 MIU/mL (8.37 log copies/mL). Repeat CSF also positive for JC virus at 48 IU/mL (1.7 log copies/mL).
In discussion between the patient's neurology and respiratory teams, a regular infliximab regimen was started to treat sarcoidosis and manage the PML.
One year following treatment
Imaging at one year of treatment shows a good and consistent intracranial response. Right frontal biopsy track. There is residual white matter signal abnormality, but this has been regressing on follow up. No new enhancement or rDWI (FLAIR imaging only uploaded for reference). ACE 86/100.
Case Discussion
Progressive multifocal leukoencephalopathy (PML) can be considered in patients with confluent white matter changes, and usually in patients with a degree of immunosuppression.
With the background of pulmonary sarcoidosis and recent azathioprine therapy, there were a number of potential triggers, although the disease clinically and radiologically worsened following cessation of AZA.
Despite several CSF samples being negative for JC virus, PML remained the favoured diagnosis and the decision was made to proceed to biopsy to confirm this, with positive results on both PCR and microscopy.
A good clinical and radiological response was seen following infliximab therapy, which has been used in sarcoidosis associated PML cases (reference available at https://doi.org/10.1093/braincomms/fcab292).
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