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BRIEF COMMUNICATIONS: C. Zucca, S. Binda, R. Borgatti, F. Triulzi, L. Radice, C. Buttè, P. E. Barkhaus, and M. Barbi Retrospective diagnosis of congenital cytomegalovirus infection and cortical maldevelopment Neurology 2003; 61: 710-712 [Abstract] [Full text] [PDF]

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Reply to Numazaki

Claudio Zucca, Renato Borgatti, Lucia Radice   (11 November 2003)

Retrospective diagnosis of congenital cytomegalovirus infection and cortical maldevelopment

Kei Numazaki   (5 November 2003)

Reply to Numazaki 11 November 2003
Claudio Zucca, I.R.C.C.S. "E. Medea" Via Don L. Monza 20 - 23842 - Bosisio Parini (LC) - ITALY, Renato Borgatti, Lucia Radice Send Correspondence to journal: Re: Reply to Numazaki zucca{at}bp.lnf.it Claudio Zucca, et al.	We thank Dr. Numazaki for his comments and are pleased that he agrees with our data and observations. [1] We agree with Dr. Numazaki's statements about CMV congenital infections and diagnosis, in particular with the last sentence: "Entirely new approaches to prevention and treatment of CMV infections of CNS are necessary, including antiviral interventions and the development of a vaccine strategy". We would like to clarify that we did not conclude that detection of viral DNA in DBS is always necessary for proof of congenital CMV infection in MCD patients. That is true only when MCD is diagnosed after the first three weeks of life. In those cases, isolation of CMV (or detection of viral protein or nucleic acid) in urine, saliva or blood does not allow distinction between infection contracted during fetal development vs infection occurring at birth or thereafter. In these cases, PCR analysis of CMV DNA in dried blood spot is necessary for diagnosis of CMV congenital infection. References 1. Zucca C, Binda S, Borgatti R, Triulzi F, Radice L, Butte C, Barkhaus PE, Barbi M. Retrospective diagnosis of congenital cytomegalovirus infection and cortical maldevelopment. Neurology 2003; 61: 710-712.
Retrospective diagnosis of congenital cytomegalovirus infection and cortical maldevelopment 5 November 2003
Kei Numazaki, Sapporo Medical University School of Medicine S.1 W.16 Chuo-ku, Sapporo, 060-8543 Japan Send Correspondence to journal: Re: Retrospective diagnosis of congenital cytomegalovirus infection and cortical maldevelopment numazaki{at}sapmed.ac.jp Kei Numazaki	Zucca et al [1] used dried blood spots (DBS) test for detection cytomegalovirus (CMV) DNA to assess ten patients with malformation of cortical development (MCD) and four were positive. They concluded that detection of viral DNA in DBS is necessary for proof of congenital CMV infection in MCD patients. The prevalence of congenital CMV infection varies between different populations (0.2-3.0%). Only ~5% of the infants with congenital CMV infection have typical cytomegalic inclusion disease, another 5% have atypical involvement, and the remainder (90%) are asymptomatic at the time of delivery. Even asymptomatic at birth, 5 to 17% of infants with these asymptomatic congenital CMV infections will develop progressive sensorineural hearing loss or other neurodevelopmental difficulties within first 4 years of life. [2] We screened for congenital CMV infection in Japan. [3] Congenital CMV infection was diagnosed with a successful virus isolation test in urine or saliva from infants within the first week of life. We screened 13 patients born in Sapporo with MCD (eight girls and five boys), aged less than 5 years for congenital CMV infection. Diagnosis of MCD was established in all cases using MRI (five cortical dysplasia, three lissencephaly, three heterotropic gray matter, one polymicrogyria and one schizencephaly). Only one patient with lissencephaly was positive for CMV. A clinical diagnosis of CMV infection of CNS is difficult and rapid and accurate laboratory diagnosis is required for appropriate patient management. 　Iannetti et al [4] reported the possibility that CMV infection had some role in the complex multifactorial pathogenesis of schizencephaly. It was also reported that CMV localized on the glial anlage in the germinal matrix might induce destructive processes, affecting the radial glial guides with anomalous neuronal migration. PCR assay provided a sensitive method to diagnose congenital CMV infection. [5] The diagnosis of CMV disease of CNS can be defined as the presence of the following criteria; positive CMV cultures or viral DNA from clinical specimens; presence of characteristic cytomegalic inclusion bodies; and positive antigenemia test in blood or CSF leukocytes and presence of specific antibodies to CMV in serum or CSF. The pathogenesis of CMV-induced damage to the fetal CNS including cortical maldevelopment is not clear and effective therapy unexplored. New approaches to prevention and treatment of CMV infections of CNS are necessary, including antiviral interventions and the development of a vaccine strategy. References 1. Zucca C, Binda S, Borgatti R et al. Retrospective diagnosis of congenital cytomegalovirus infection and cortical maldevelopment. Neurology 2003; 61: 710-712. 2. Demmler GJ. Congenital cytomegalovirus infections. Seminars in Pediatric Infectious Diseases 1997; 5: 52-55. 3. Numazaki K, Chiba, S. PCR detection of cytomegalovirus DNA in serum as test for congenital cytomegalovirus infection. J Clin Microbiol　1996; 34: 1971-1972. 4. Iannetti P, Nigro G, Spalice A, Faiella A, Bonchinelli E. Cytomegalovirus infection and schizencephaly: case reports. Ann Neurol 1998; 43: 123-127. 5. Nelson CT, Istas AS, Wilkerson MK, Demmler GJ. PCR detection of cytomegalovirus DNA in serum as a diagnostic test for congenital cytomegalovirus infection. J Clin Microbiol 1995; 33: 3317-3318.