Progressive Cerebellar Ataxia After Natalizumab Treatment

A 47-year-old woman with a history of relapsing-remitting multiple sclerosis (MS) receiving natalizumab therapy sought a second opinion regarding a recent diagnosis of secondary progressive disease. She was first diagnosed with multiple sclerosis 8 years earlier. While taking natalizumab, she was monitored for the development of antibodies to JC polyoma virus. Nine months before our evaluation, anti-JC polyoma virus antibodies became positive, with an increased index of 1.1. Given sustained remission, she was continued on natalizumab with increased surveillance and a plan to switch to a different disease-modifying therapy after 24 months. Five months later she noted subacute onset of slurred speech and right upper extremity incoordination. Over the next 4 months she continued to have clinical decline. On examination she had moderate ataxic dysarthria and right greater than left appendicular ataxia. She relied on a wheelchair for transportation and required 1-person assist to stand. Reflexes were brisk with bilateral Babinski sign. This patient with relapsing-remitting multiple sclerosis on natalizumab had a new subacute progressive cerebellar syndrome without radiographic evidence of disease activity. Repeated magnetic resonance imaging showed worsening cerebellar atrophy, right sided greater than left sided, and evolving T2 hyperintensity in the brainstem without enhancement or mass effect. JC polyoma virus polymerase chain reaction was positive. The patient was diagnosed with JC polyoma virus granule cell neuronopathy. Natalizumab was discontinued, and she was treated with 4 of 5 planned cycles of plasma exchange. After her 4th cycle, worsening symptoms developed. Magnetic resonance imaging showed gadolinium enhancement in the brainstem supportive of immune reconstitution inflammatory syndrome. She received high-dose intravenous methylprednisolone followed by a prednisone taper. Her disability progression stabilized. JC polyoma virus central nervous system infection, 1 of several infections reported among treated patients with multiple sclerosis, occurs almost exclusively in immunosuppressed patients, including those receiving disease-modifying therapy for multiple sclerosis.

Elevated levels of Merkel cell polyoma virus in the anophthalmic conjunctiva

The human ocular surface hosts a paucibacterial resident microbiome and virome. The factors contributing to homeostasis of this mucosal community are presently unknown. To determine the impact of ocular enucleation and prosthesis placement on the ocular surface microbiome, we sampled conjunctival swabs from 20 anophthalmic and 20 fellow-eye intact conjunctiva. DNA was extracted and subjected to quantitative 16S rDNA PCR, biome representational karyotyping (BRiSK), and quantitative PCR (qPCR) confirmation of specific organisms. 16S ribosomal qPCR revealed equivalent bacterial loads between conditions. Biome representational in silico karyotyping (BRiSK) demonstrated comparable bacterial fauna between anophthalmic and intact conjunctiva. Both torque teno virus and Merkel cell polyoma virus (MCPyV) were detected frequently in healthy and anophthalmic conjunctiva. By qPCR, MCPyV was detected in 19/20 anophthalmic samples compared with 5/20 fellow eyes. MCPyV copy number averaged 891 copies/ng in anophthalmic conjunctiva compared with 193 copies/ng in fellow eyes (p < 0.001). These results suggest that enucleation and prosthesis placement affect the ocular surface flora, particularly for the resident virome. As MCPyV has been shown to be the etiologic cause of Merkel cell carcinoma, understanding the mechanisms by which the ocular surface regulates this virus may have clinical importance.

Evaluation of Renal Biopsy for Transplant: The Significance of Whole Slide Imaging (WSI) in Telepathology

Introduction/Objective Percutaneous Renal biopsy remains a gold standard technique to provide diagnostic and prognostic information post kidney transplantation. Recently Whole slide imaging (WSI) telepathology systems have been widely used for clinical, education and research purposes. Our aim was to examine reliability and accuracy of WSI telepathology service in the pathology diagnosis of biopsy specimens from transplanted kidney. Methods At our institution we have two renal pathologists. They utilize WSI telepathology service with Aperio scanner for rapid initial assessment of the transplant renal biopsy specimens. We retrospectively reviewed reports of all transplant renal biopsies which were examined remotely utilizing WSI telepathology service and compared the results for initial versus final diagnoses. Results In period from Jan 2019 to April 2020 total 160 renal transplant biopsies were evaluated remotely utilizing the WSI scanner. The diagnosis was divided in 4 subcategories as reperfusion injury, rejection (Antibody mediated or T cell mediated), mixed inflammation-favor infection and Polyoma virus infection. There were 48 cases of reperfusion injury; 5 cases of polyoma virus infection, 37 cases of rejection and 28 cases with mixed inflammation and 42 cases with no significant histopathologic findings. There was no discrepancy between the preliminary and final diagnosis for all 160 cases. The ancillary studies including special stains and electron microscopy added to the final diagnosis or confirmed the preliminary diagnosis. Conclusion WSI telepathology is a reliable and simple method to rapidly review transplant kidney biopsies. The ability to transmit images from hospitals to pathologists with WSI scanner has the potential for not only an accurate assessment of the rejection but also for additional histopathological findings. Digital pathology enhances the clinical usefulness of immediate assessments of transplant biopsy samples and also provides a platform to share the scanned images with clinicians which also can be utilized for education of trainees.

Bk Polyoma Virus Nephropathy In An Immunocompromised Host.

Background: Post-transplant Lymphopoliferative disorders(PTLD) are a well known late complication after solid organ transplantation including renal transplant. Among others, graft failure due to reactivation of BK polyoma virus in the grafted kidney is also a well recognized complication but tends to present early in the first several months after transplant. Case: Here we present the case of PTLD Burkitt's lymphoma(BL-PTLD) in a renal transplant patient who was successfully treated with multiagent chemo-immunotherapy but later developed BK polyoma virus nephropathy(BKVN) with graft failure only after completion of her systemic therapy for lymphoma and 7 years after transplant. Relevant literature is reviewed. Conclusion: In this case, reactivation and progression of BKVN was most likely associated with immunosuppression from chemoimmunotherapy for her BL–PTLD unlike early graft failures associated with BKVN.

Hyperpigmentation Associated with the Use of Topical Cidofovir for Treatment of Trichodysplasia Spinulosa in an Immunosuppressed Adult: Case Report and Review of the Literature

Trichodysplasia spinulosa (TS) is a rare, opportunistic infectious skin disease caused by the polyoma virus. Clinically, TS is characterized by follicular papules, keratin spicules, and alopecia most classically in a midfacial distribution. Since its discovery in 2010, no standard of treatment has been established, though use of oral acitretin, valganciclovir, lefludomide, topical cidofovir, physical extraction, and modification of immunosuppressive medications have been reported in the literature. We describe the case of a 52-year old female with a painful midfacial eruption and alopecia of the bilateral eyebrows ultimately diagnosed with TS and treated with topical cidofovir 3%. Though the TS eruption resolved, treatment resulted in hyperpigmentation of the affected area. Hyperpigmentation associated with cidofovir use has been reported in cases of molluscum contagiosum, however, no such association has been described in the treatment of TS to our knowledge. Therefore, we report this case to highlight an underreported adverse effect of topical cidofovir in the setting of this rare disease.