Look in the Back (Slides)

The procedure was a repeat dilated ophthalmoscopy, which now demonstrated bilateral chorioretinal whitening and retinal necrosis. A vitreous tap disclosed 6,900,000 copies/mL of varicella zoster (VZV) PCR (upper limit of normal 3,160 copies/mL). The following day, cerebrospinal PCR returned an elevated VZV PCR titer (22,000 copies/mL). He was treated with IV acyclovir and intravitreal foscarnet, but died 8 weeks later. Autopsy was not performed. Transaxonal spread of VZV to the meninges and arterial vessel walls accounts for the abnormalities in our patient, except for the retinal necrosis, whose pathogenesis remains unexplained. (1-4) High-definition MRI has recently been reported to disclose intracranial vascular wall enhancement in VZV, (1) which was evident even on traditional MRI in our patient, and which led to the correct diagnosis. The initial retinal examination had suggested NHL retinopathy. However, VZV retinal necrosis can share features with other causes of retinal whitening. Retinal findings can become more classically necrotic over time, highlighting the need for repeat fundus examination.

Look In The Back Tatiana Deveney, MD, Aristides Capizzano, MD and Jonathan Trobe, MD Department of Ophthalmology and Visual Sciences (Kellogg Eye Center) Department of Neurology Department of Radiology (Neuroradiology) University of Michigan No financial disclosures History • 59 year old man with Graves disease (treated remotely with RAI), coronary artery disease • Proptosis and diplopia for at least 4 months • Treated with intravenous and oral corticosteroids, orbital x-irradiation • Three weeks before presentation to us, declining vision, new bilateral hearing loss, lower extremity weakness, and urinary retention • Referred for orbital decompression Medications • aspirin • atorvastatin • hydrochlorothiazide • levothyroxine • lisinopril • propranolol • prednisone (40 mg daily) • tamsulosin Our Clinical Exam Limited ductions in all directions in both eyes Our Clinical Exam OD OS 20/80, PH NI 20/200, PH NI 19 mmHg 22 mmHg 3 to 2, no APD 3 to 2, no APD Slit Lamp Moderate punctate staining of cornea Moderate punctate staining of cornea Vitreous Normal Normal Fundus Multifocal white/yellow subretinal lesions Multifocal white/yellow subretinal lesions Visual Acuity (cc) Intraocular Pressure (IOP) Pupils • Drowsy • Bilateral sensorineural hearing loss • Bilateral lower extremity weakness • Diminished lower extremity deep tendon reflexes Imaging Enlarged extraocular muscles without compression of the apical optic nerves Imaging Post Contrast T1 MRI shows leptomeningeal enhancement of both 7th/8th nerve complexes (blue arrow) and dura Imaging Post Contrast T1 MRI shows perineural enhancement of both optic nerves (blue arrow) Imaging Axial Post Contrast T1 MRI shows enhancement of the cauda equina (yellow circle) and leptomeningeal enhancement along the brainstem and spinal cord (yellow arrow) Imaging Axial DWI (left) and ADC (right) MRI shows restricted diffusion in the right basal ganglia (top) and left fornix (bottom) Imaging Post Contrast Coronal T1 MRI shows enhancement of the first branch of the middle cerebral artery (blue arrow) Imaging Post-Contrast Axial T1 again shows perivascular enhancement along right M1 and A1 (yellow arrow) and in the basal ganglia (likely within perivascular spaces) Lumbar Puncture • Normal opening pressure • WBC 577 (78% lymphocytes), RBC 10,000 • Protein 348 mg/dL • CSF cytology and cytometry negative This process is… 1. 2. 3. 4. 5. Neoplastic Inflammatory Ischemic Infectious None of the above Summary of Clinical Manifestations • Brain parenchymal stroke • Large vessel vasculitis • Cranial neuritis • Meningitis • Retinal abnormalities Further Evaluation Representative Image Perrone et al. Neurol Neuroimmunol Neuroinflamm. 2019. 6;4: e582 What would you do now? 1. 2. 3. 4. Repeat lumbar puncture (high volume) Repeat MRI Meningeal biopsy Vitreous tap Further Evaluation • Dilated ophthalmoscopy: Bilateral chorioretinal whitening and retinal necrosis • Vitreous tap: 6,900,000 copies/mL zoster PCR • Spinal fluid: 22,000 copies/mL zoster PCR Multiple Nervous System Manifestations of Zoster Clinical Course • Treated with IV acyclovir and intravitreal foscarnet • Died 8 weeks later • No autopsy performed Zoster and the Nervous System • Transaxonal spread to meninges and arterial vessel wall causes meningoencephalitis, neuritis, and stroke • Not sure how zoster gets into the retina Nagel MA, Gilden D. Neurological Complications of Varicella Zoster Virus Reactivation. Cur Opin Neurol. 2014; 27:356-360. Savoldi F, Kaufmann TJ, Flanagan EP, Toledano M, Weinshenker BG. Elsberg syndrome: A rarely recognized cause of cauda equina syndrome and lower thoracic myelitis. Neurol Neuroimmunol Neuroinflamm. 2017; 4: e355. Zoster Vessel Wall Enhancement • Can see vasculitis best on submillimeter post-contrast MRI ("black blood") sequences • But can also see on traditional MRI, as in our case Shah J, Poonawala H, Keay S, Serulle Y, Steven A, Gandhi D, Cole J. Varicella-Zoster Virus Vasculopathy: A Case Report Demonstrating Vasculitis using Black-Blood MRI. J Neurol Neurophysiol. 2015; 6:6 Song JW, Ojeda S, Romero JM. High resolution vessel wall MRI and vasculopathy related to herpes zoster ophthalmicus. Clin Imaging. 2018; 50:336-339. English SW, Carabenciov ID, Lehman VT, Petty GW, Scharf EL. Zoster vasculopathy surveillance using intracranial vessel wall imaging. Neurology: Clinical Practice. 2019; 9:66:4662-464 Zoster and the Retina • Zoster retinal necrosis shares features with other infectious processes and can also be confused with lymphoma • Zoster retinal necrosis can evolve to a more classic picture Say EA, Knupp CL, Gertsch KR, Chavala SH. Metastatic B-cell lymphoma masquerading as infectious retinitis and vasculitis. Oncol Lett. 2012; 3:1245-1248. Karma A, von Willebrand EO, Tommila PV, Paetau AE, Oskala PS, Immonen IJ. Primary Intraocular Lymphoma: Improving the Diagnostic Procedure. Ophthalmology. 2007; 114: 1372-1377. Summary 1. Zoster causes central and peripheral nervous system damage by two mechanisms: vasculitic infarction and inflammation 2. Zoster is a common-if forgotten-cause of these phenomena in immunocompromised hosts 3. Zoster retinitis can initially resemble lymphoma until zoster retinitis evolves to necrosis 4. MRI, especially with "black blood" protocol, is a useful tool in displaying large vessel wall enhancement in zoster vasculitis