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Page 2 of 7 Inamullah et al. Neuroimmunol Neuroinflammation 2018;5:3 I http://dx.doi.org/10.20517/2347-8659.2017.61

immunosuppressed, the JC virus can spread to the central nervous system, and cause a life-threatening
severe neurological illness.

Patients with PML usually have gradually worsening neurological deficits including encephalopathy, motor
deficits, and visual symptoms. PML lesions are generally in the white matter, and magnetic resonance
imaging (MRI) typically shows that these lesions have no mass effect and no contrast enhancement.
Diagnosis can be established by confirming JC virus DNA in the cerebrospinal fluid (CSF) along with typical
imaging, but definitive diagnosis requires brain biopsy with the histopathologic triad of demyelination,
bizarre astrocytes, and enlarged oligodendroglial nuclei coupled with techniques to show the presence of JC
[2]
virus . PML is an incredibly rare condition. It occurs almost always in patients with a suppressed immune
system, either from medications or a preexisting illness such as human immunodeficiency virus (HIV),
chronic lymphocytic leukemia, or lymphoma. Several immune suppressing medications have been known
to cause PML, most notably natalizumab and rituximab. Hydroxychloroquine (also known as plaquenil) is
a medication frequently used to suppress the immune system that has not been previously associated with
PML.

CASE REPORT
Patient D is a 65-year-old man with a history of asthma, benign prostatic hyperplasia, pre-diabetes, and
dermatologic sarcoidosis who presented to the Duke General Neurology service in July of 2017 with about
6 months of rapidly worsening right-sided weakness, facial weakness, and cognitive decline. He had been
taking hydroxychloroquine 200 mg daily to treat his dermatologic sarcoidosis since September of 2014 (about
3 years prior to presentation). No other immunosuppressive drugs have been shown in medical records. His
other home medications were paxil, aspirin, vitamin D, montelukast, and flomax. His rheumatologist also
gave him a prolonged steroid taper after his symptoms first began.

In mid-March, he initially noticed right foot numbness and weakness and went to his podiatrist and
primary care doctor, who both documented normal neurologic examinations. In early April, the patient was
seen by his rheumatologist, who reported right foot drop, prescribed an oral steroid course, and referred
him to a neurologist, who documented weakness and decreased sensation to pinprick in the distal right
lower extremity. In early May, he was noted to have involvement of his proximal right lower extremity, with
mild weakness of hip flexion and extension, moderate weakness of knee flexion and extension, and almost
complete inability to dorsiflex or plantarflex his right foot. In early July, he followed up with his neurologist
and reported continued progression of weakness, including his right arm. On examination, he had a right
pronator drift with mild weakness of his right hand intrinsic muscles and difficulty with fine motor skills, as
well as mild weakness of hip flexion, moderate weakness of knee flexion and extension, and severe weakness
of dorsiflexion and plantarflexion on his right side. He was walking with a walker and dragging his right
foot, and he had fallen several times. He was also noted to have flattening of his right nasolabial fold.

Due to his multifocal and rapidly progressive motor symptoms, his preliminary diagnosis was a variant of
motor neuron disease. He initially received a broad laboratory work-up, which was unimpressive including
negative testing for HIV. Next, due to concern for motor neuron disease, electromyography was performed
and showed increased insertional activity in the majority of muscle groups tested with generalized reduction
in activation, concerning for a central nervous system etiology. Lumbar puncture was performed and was
unremarkable, including negative JC virus polymerase chain reaction (PCR). MRI’s of the cervical, thoracic,
and lumbar spines were normal. Brain MRI performed revealed enlargement of non-enhancing subcortical
and periventricular T2 hyperintensities [Figure 1] with Wallerian degeneration [Figure 2].

There was concern for neuro-sarcoidosis due to his history of dermatologic sarcoidosis despite the lack of
contrast enhancement on the MRI lesions. Computed tomography scan of the chest revealed supraclavicular,