Clinicopathologic Conference (CPC) 03/17/17 Neurology Resident: Pouria Moshayedi Pathologist: Ronald Hamilton

History 85 year old male with PMHx of HTN, HLD, A-fib (on eliquis), Prostate Ca, hypothyroidism, hearing loss and idiopathic pulmonary fibrosis (on Esbriet and steroid), who presented from his SNF with a 4 week history of right arm pain. Right arm pain started after he developed a vesicular rash throughout his entire RUE. Pain started after increasing dose of prednisone for his SoB and PF. Diagnosed with shingles of the RUE; treated with valacyclovir/ Valtrex. Pain was intermittent, spontaneously occurring Q5-15 min, crippling, sharp, burning & shooting from finger to his shoulder. Refractory to treatment with pregabalin, doluxetine, and nerve block. Artistic work by Robert Russin, who had post-herpetic neuralgia

History ROS was positive for RUE pain and decreased hearing in right ear PMH: A-fib, Prostate Ca (s/p radiation seeds), HTN, HLD, Hypothyroidism, IPF, Appendectomy, Lumbar fusion Medications: Tylenol, pregabalin, doluxetine, Esbriet, prednisone, dig, dilt

Examination Labs: Mental Status: Alert, oriented x2. Language intact. CN: WNL Motor: Right foot drop for 2-3 months Sensory: Pain followed C5-C6 distribution. Vibration and pinprick intact in RUE. Hyperesthesia and distorted sensation when tested during spells. Reflex: No exaggerated or pathologic reflex Coordination: Mild dysmetria on right GAIT: UTA Labs: WBC 13 (Bandemia of 6-8%). CRP 10. ESR 63. Neg NMO ab. CSF: Nl OP. WBC 41 (99% Lym), RBC 3, glu 90, protein 54. VZV PCR undetermined. EBV, CMV, HSV1/2 PCRs negative. Neg VDRL and Lyme abs. Positive anticomplement immunofluorscence for VZV. Negative VZV IgM.

Radiology – Sagittal T2 No definite enhancement

Radiology – Axial T2 R

Examination Labs: Mental Status: Alert, oriented x2. Language intact. CN: WNL Motor: Right foot drop for 2-3 months Sensory: Pain followed C5-C6 distribution. Vibration and pinprick intact in RUE. Hyperesthesia and distorted sensation when tested during spells. Reflex: No exaggerated or pathologic reflex Coordination: Mild dysmetria on right GAIT: UTA Labs: WBC 13 (Bandemia of 6-8%). CRP 10. ESR 63. Neg NMO ab. CSF: Nl OP. WBC 41 (99% Lym), RBC 3, glu 90, protein 54. VZV PCR undetermined. EBV, CMV, HSV1/2 PCRs negative. Neg VDRL and Lyme abs. Positive anticomplement immunofluorscence for VZV. Negative VZV IgM.

Gel electrophoresis on PCR amplified VZV – CSF Sample C C Courtesy of Dr. Charles Rinaldo

Clinical Course Pain service recommended Tylenol, ibuprofen and Lidoderm. Increasing doluxetine and pregabalin, and adding oxcarbazepine led to some improvement. Started acyclovir after CSF pleocytosis. Transferred to Medical ICU on day 3 following respiratory distress. Started on antibiotics for possible PNA (question of VZV pneumonitis?). Made CMO. Passed away on hospital day 6.

Differential Diagnosis Pain: Post-herpetic neuralgia Cord signal change/CSF pleocytosis: VZV myelitis: No sensory or motor finding suggesting myelopathy VZV radiculitis Metabolic: B12/D/E/Cu/B1 deficiency Other infections: not sent for fungal culture. Other viral/lyme studies neg Vascular: infarction and malformations/fistula unlikely with normal exam Demyelination/autoimmune: unlikely for his age. NMO ab neg. Idiopathic myelopathy Chronic signal change, clinically insignificant, related to possible trauma

Predicted Pathology – Optical Microscope If VZV Myelitis: Perivascular inflammation and vasculitis Necrosis Meningitis Kleinschmidt-DeMasters and Gilden, Arch Pathol Lab Med 2001

Predicted Pathology – Electron Microscope Cowdry Type A intranuclear inclusion bodies in oligodendrocytes Intracytoplasmic Virion and capsid inclusion bodies in white matter cells. Hogan and Krigman, Arch Neurol 1973

CD68

CS Tract CD88 CD68 CD4

Dorsal Root Entry CD8 CD68 CD4

Anti-VZV

CD68