Unlike many forms of SNHL cCMV may
Unlike many forms of SNHL, cCMV may be treatable. The antiviral drug valganciclovir (VGCV) has been proposed to improve hearing, speech, and language outcomes associated with this infection . A recent publication from the CASG (Collaborative Antiviral Study Group) reported that a six-month course of VGCV therapy provides a modest improvement in hearing and neurocognitive outcomes when compared to a shorter six-week course of therapy . While this data is promising, there is little information regarding the long-term hearing outcomes following VGCV therapy. Within our own institution, we have noticed that some children with symptomatic cCMV previously treated with VGCV will go on to develop worsening hearing loss years later. These findings have prompted a more in-depth evaluation of the hearing outcomes among these patients to determine what the long-term hearing outcomes are for children with symptomatic cCMV-related disease.
Materials and methods A retrospective chart review of symptomatic cCMV patients treated with VGCV was completed. Patients were deemed symptomatic if they had one or more of the following conditions related to their cCMV infection: thrombocytopenia, petechiae, hepatomegaly, splenomegaly, intrauterine growth restriction, hepatitis, microcephaly, intracranial calcifications, abnormal cerebrospinal fluid indexes, or chorioretinitis. All patients were confirmed to have cCMV infection through Caspase-3/7 Inhibitor or saliva specimens within the first three weeks of life, or dried-blood spot testing as part of the metabolic screening during the first days of life. All infants diagnosed with symptomatic congenital cytomegalovirus infection were offered VGCV therapy. This recommendation is based on two randomized clinical trials that demonstrated a neurocognitive and hearing benefit from this treatment [7,11]. Children were initially offered a six-week course at 16 mg/kg bid. After the 2015 Kimberlin et al. paper demonstrated greater efficacy with a longer treatment course of six months, this approach was offered . The outcome index of treatment was primarily speech and language, specifically receptive and language composite scores. While the therapeutic purpose of VGCV therapy was the ability to have some recovery or improvement in hearing. Patients were then followed with regular audiologic assessments, with an average of 5.8 assessments being performed on each study participant. The primary endpoint was the change between baseline and follow-up in the hearing scores corresponding to the best ear at each audiologic follow-up time point. This measure was used as a functional assessment in daily living. For example, a child with mild hearing loss in one ear and profound loss in the contralateral ear will function like a child with a mild hearing impairment . Secondary endpoints included change in mean thresholds for both the right and left ear, time to hearing deterioration after treatment, and the proportion of best versus worse ear that deteriorates first. The hearing score in each ear is defined by averaging the minimum response levels at two frequencies (2.0 kHz and 4.0 kHz). Clinically significant worsening of hearing was defined as the occurrence of either: a) 10 dB or greater increase in minimum response level (MRL) at both 2 and 4 kHz, b) 15 dB or greater increase at either frequency, or c) cochlear implantation. A paired-sample t-test was used to evaluate differences in the mean change of hearing scores. The institutional review board (IRB) at our institution approved our study protocol.
Results Sixteen symptomatic cCMV infected children who underwent treatment with VGCV were included in Archaea study, of which 10 (62.5%) patients were female and 6 (37.5%) were male. A total of nine patients were started on therapy before one month of age. While seven patients were started on therapy after one month of age, with an average start of therapy at 13.3 months of age among those patients. Approximately one-third of children had two or more of the major symptoms associated with cCMV, with neurologic findings including gliosis, intracranial calcifications, microcephaly, cortical dysplasia, cystic changes and demyelination. None of the patients included in the study had normal hearing at baseline. All patients were treated with VGCV therapy and the average duration of treatment was 92.7 days. The breakdown on the length of therapy is as follows: six patients less than six weeks therapy, seven patients between six weeks and six months, and three patients for more than six months. Average audiological follow-up was 3.2 years (range 0.3–10.0 years). Approximately 37.5% of patients were followed for at least five years. A summary of the patient characteristics can be seen in Table 1.