Contributed by Cheng-Hsuan Chiang, MD, PhD1, Charleen T. Chu, MD, PhD1,2, and Clayton A. Wiley, MD, PhD1,2
1Department of Pathology, 2Division of Neuropathology, University of Pittsburgh School of Medicine, Pittsburgh, PA
The patient was a 67-year-old male with a 39-year history of relapsing multiple sclerosis (MS). He had been treated with 54 doses of Natalizumab (Tysabri) during the past 5 years. Due to new onset of neurological symptoms including bilateral upper extremity dysmetria, slurred speech and choking, MRI of the brain was performed. FLAIR/T2 showed longstanding lesions in the cerebral periventricular regions bilaterally (Fig. 1) and new hyperintense foci in bilateral cerebellar white matter extending into the middle cerebellar peduncles (Fig. 2). The larger left-sided cerebellar lesion measured 2.7 x 2.4 cm. The cerebral and cerebellar lesions had well-defined borders with no significant mass effect and minimal peripheral contrast enhancement. CSF analysis showed an opening pressure of 12 mm H2O, a normal differential count and glucose level with an elevated protein level, elevated IgG index and oligoclonal bands. HHV6, HSV1, HSV2, and cytology studies were negative. The patient was admitted. Natalizumab was discontinued, and plasmapheresis and IV Dexamethasone initiated. Despite the treatment, his neurological condition continued to deteriorate. He was discharged to hospice and expired 8 days afterward.
AUTOPSY NEUROPATHOLOGY FINDINGS
Autopsy revealed multiple grossly well-defined lesions in the bilateral cerebral periventricular areas (Fig. 3), cerebellar white matter (Fig. 4) and gray and white matter of the spinal cord. Cerebellar lesions appeared softened and depressed after sectioning.
MICROSCOPIC NEUROPATHOLOGY FINDINGS
LFB/CV stains demonstrated multiple well-defined periventricular chronic demyelinating lesions (Fig. 5), and multiple areas of demyelination in both gray and white matter of the spinal cord with mild loss of motor neurons in demyelinated gray matter areas (Fig. 6). LFB/H&E stain showed chronic demyelination of the right optic nerve (Fig. 7). Periventricular and spinal cord demyelinating lesions showed preserved axons (Fig. 8) with minimal inflammation (Fig. 9) and few macrophages (Fig. 10). Lightly myelinated axons were present in the periphery of the lesions (Fig. 11). The cerebellar lesions showed significant areas of demyelination with indistinct borders (Fig. 12). Abundant myelin debris was seen in the extracellular space and within macrophages (Fig. 13). CD68 immunostain demonstrated abundant macrophages (Fig. 14). A marked CD3-positive, CD8-positive T lymphocyte infiltrate was also present (Fig. 15). What additional stain is required for the diagnosis of the cerebellar lesions? What are your final diagnoses?