25572898 Visualization

A 42 Age year Age - old Age man Sex with chronic Detailed_description lymphocytic Disease_disorder leukemia Disease_disorder underwent allogeneic Detailed_description bone Therapeutic_procedure marrow Therapeutic_procedure transplant Therapeutic_procedure in September Date 2013 Date .
The graft Coreference was mismatched Detailed_description at Detailed_description a Detailed_description single Detailed_description human Detailed_description leukocyte Detailed_description antigen Detailed_description allele Detailed_description ( DQB1 Detailed_description ), and was T Detailed_description - cell Detailed_description depleted Detailed_description using in Detailed_description vivo Detailed_description alemtuzumab Medication .
He engrafted Therapeutic_procedure on day Date 12 Date after transplant Therapeutic_procedure .
Aside from persistent Detailed_description lymphopenia Sign_symptom and diarrhea Sign_symptom from norovirus Disease_disorder infection, his posttransplant Diagnostic_procedure course Diagnostic_procedure was unremarkable Lab_value until mid Date - October Date when he developed tinnitus Sign_symptom and rapidly Detailed_description progressive Detailed_description sensorineural Disease_disorder deafness Disease_disorder , resulting in subtotal Detailed_description hearing Sign_symptom loss Sign_symptom bilaterally Detailed_description ( >95 Lab_value dB Lab_value ) over Duration 2–3 weeks Duration .
Brain Biological_structure magnetic Diagnostic_procedure resonance Diagnostic_procedure imaging Diagnostic_procedure ( MRI Diagnostic_procedure ) was unremarkable, as was cerebrospinal Diagnostic_procedure fluid Diagnostic_procedure ( CSF Diagnostic_procedure ) analysis ( 4 Lab_value leukocytes/µL Lab_value with 50% Lab_value neutrophils Diagnostic_procedure and 50% Lab_value lymphocytes Diagnostic_procedure , 6 Lab_value red Lab_value blood Lab_value cells/µL Lab_value , glucose Diagnostic_procedure 2.4 Lab_value mmol/L Lab_value [normal range, 2.2–4.7 mmol/L], protein Diagnostic_procedure 61 Lab_value mg/dL Lab_value [normal range, 15–45 mg/L], absence Lab_value of oligoclonal Diagnostic_procedure bands Diagnostic_procedure ).
Viral Detailed_description polymerase Diagnostic_procedure chain Diagnostic_procedure reaction Diagnostic_procedure (PCR) testing of CSF Detailed_description was negative for enterovirus Disease_disorder and herpesvirus Disease_disorder infection.
The patient was treated empirically with high-dose valacyclovir Medication , broad-spectrum antibiotics Medication , and 2 Dosage g/kg Dosage intravenous Administration immunoglobulin Medication ( IVIG Medication ).
Despite these interventions, he developed new symptoms of central dyspnea Sign_symptom , postural Detailed_description hypotension Sign_symptom , nausea Sign_symptom , and gradually Lab_value worsening Lab_value balance Diagnostic_procedure .
Repeat neurological Diagnostic_procedure assessment Diagnostic_procedure confirmed persistent Detailed_description vestibulocochlear Disease_disorder dysfunction Disease_disorder 6 Date weeks Date after Date symptom Sign_symptom onset.
By mid Date - December Date , the patient had become increasingly withdrawn Sign_symptom , irritable Sign_symptom , and intermittently Detailed_description agitated Sign_symptom .
He remained lymphopenic Sign_symptom ( lymphocytes Diagnostic_procedure 0.54 Lab_value × Lab_value 106/μL Lab_value [normal range, 1.2–3.6 × 106/μL]).
MRI Diagnostic_procedure scans of the brain Biological_structure were unremarkable Lab_value , as was serum Detailed_description testing Detailed_description for antineuronal Diagnostic_procedure antibodies Diagnostic_procedure ; an electroencephalogram Diagnostic_procedure revealed only diffuse encephalopathy Disease_disorder .
Given continued suspicion for a viral Disease_disorder etiology, the patient was treated with high Dosage - dose Dosage glucocorticoids Medication and again with IVIG Medication .
He began refusing fluids Activity , food Activity , and medication Medication , and was detained Clinical_event under the UK Detailed_description Mental Detailed_description Health Detailed_description Act Detailed_description .
Repeat MRI Diagnostic_procedure scanning showed interval development of new Detailed_description , nonenhancing Detailed_description signal Sign_symptom abnormalities Sign_symptom in both Biological_structure thalami Biological_structure and midbrain Biological_structure with cranial Biological_structure nerve Biological_structure involvement but no meningeal Biological_structure enhancement Sign_symptom (Figure ​1A).
Near Date the Date end Date of Date December Date , a frontal Biological_structure lobe Biological_structure biopsy Diagnostic_procedure was performed.
Histology Diagnostic_procedure revealed reactive Detailed_description gliosis Sign_symptom and diffuse Detailed_description infiltration Sign_symptom with CD3+/8+ Detailed_description lymphocytes Detailed_description (Figure 1B).
Extensive microbiological Diagnostic_procedure testing Diagnostic_procedure of the biopsy Detailed_description tissue Detailed_description for an infectious Detailed_description etiology Detailed_description was negative Lab_value (Supplementary Table 1).
Given the absence of a diagnosis and the patient's progressive neurological Disease_disorder deterioration Disease_disorder , CSF Detailed_description and Detailed_description brain Detailed_description biopsy Detailed_description tissue Detailed_description were analyzed in January Date 2014 Date by metagenomic Detailed_description next Diagnostic_procedure - generation Diagnostic_procedure sequencing Diagnostic_procedure ( NGS Diagnostic_procedure ) [2].
NGS Diagnostic_procedure analysis of the brain Detailed_description biopsy Detailed_description , genome Diagnostic_procedure assembly Diagnostic_procedure , and in Diagnostic_procedure situ Diagnostic_procedure hybridization Diagnostic_procedure revealed findings of neuroinvasive Detailed_description astrovirus Disease_disorder ( AstV Disease_disorder ) infection.
Despite lack of approved therapies, the patient was treated with ribavirin Medication and IVIG Medication .
However, he did not respond to these interventions, and remained in a minimally Sign_symptom conscious Sign_symptom state Sign_symptom following withdrawal of sedation Medication in March Date 2014 Date .
He eventually died Activity at the end Date of Date May Date , 4 Date months Date after Date the NGS Diagnostic_procedure diagnosis and approximately 7.5 Date months Date after Date onset of symptoms Sign_symptom .