Elsevier

Vaccine

Volume 27, Issue 13, 18 March 2009, Pages 1970-1973
Vaccine

Acute cerebellar ataxia in the Netherlands: A study on the association with vaccinations and varicella zoster infection

https://doi.org/10.1016/j.vaccine.2009.01.019Get rights and content

Abstract

Aim

Acute cerebellar ataxia (ACA, sudden onset of truncal ataxia and gait disturbances) usually follows a benign illness (25% varicella). It is also described after vaccination, like MMR and varicella zoster virus (VZV). We will establish incidence rates of (varicella related) ACA and assess the attributable risk of vaccination to ACA in the Netherlands.

Method

Data on ACA in children, following infections, like varicella, and vaccinations, obtained from prospective, active pediatric surveillance and passive surveillance on adverse events following immunizations (AEFI) were compared with hospitalization data for ataxia. Capture–recapture (CRC) method was used to estimate the burden of ACA in the Netherlands.

Results

45 children with ACA were included (44 and 1 reported by pediatric and AEFI surveillance respectively, 30 were hospitalized). Chickenpox preceded ACA in 15 cases, one case followed MMR. Of the hospitalization reports, 13 fulfilled the criteria for ACA. Using CRC the estimated number of hospitalized ACA cases was 42. For varicella related ACA, this estimate was 10, resulting in an incidence rate of 0.7:100,000 (95%CI 0.52–0.94, all cases) and 0.17:100,000 (95%CI 0.09–0.31, varicella related cases) for children under 15 years of age.

Conclusion

The incidence rates were comparable with other studies. We found no association with MMR, but chickenpox was clearly related to ACA. According to age-specific seroprevalence data the incidence rate of ACA was 5:100,000 VZV infections for children up to 5 years, compared to an ACA-reporting rate of 0.15:100,000 doses VZV-vaccine. Therefore, uptake of VZV-vaccine in the immunization programme will diminish the incidence rate of ACA.

Introduction

Acute ataxia in childhood has a wide range of causes. The differential diagnosis for acute ataxia in children is broad and includes toxicological, infectious, structural and metabolic causes [1], [2], [3].

The most common cause (40%) of childhood ataxia is acute cerebellar ataxia (ACA) with an estimated incidence of 1:100,000–500,000 children per year [4]. ACA is characterized by the acute onset of truncal ataxia and gait disturbances, sometimes combined with nystagmus or other (involuntary) eye movements [1], [3], [4], [5]. Usually ACA follows a benign (viral) illness. Varicella is preceding ataxia in about one-quarter of the cases. Other possibly related infections are Epstein Barr virus, Enterovirus, mumps, hepatitis A, and Influenza A and B [1], [6], [7], [8], [9], [10], [11], [12]. ACA sometimes follows vaccines, like measles, hepatitis B and Influenza, but a causal relationship has not been established and attributable risks are not known [1], [13], [14], [15], [16].

For varicella, ACA is the most common neurological complication, occurring in 1:4000 children under 15 years of age in the USA [3], [17], [18]. Passive postmarketing surveillance (PMS) data show a reporting rate of ACA following varicella vaccination of 1.5:1,000,000 doses [19]. The enhanced passive safety surveillance system for the National Immunization Programme (NIP) of the Netherlands occasionally receives reports of ataxia, mainly following MMR (measles, mumps, rubella) vaccination [20]. However, in most cases other possible causes of ataxia were not excluded or other viral infections coincided with the vaccinations.

Currently the uptake of varicella zoster vaccination in the NIP is under consideration in the Netherlands [21], [22], [23], [24]. Until now no information is available on incidence rates of total ACA, ACA following varicella infection and the attributable risks of MMR to ACA in the Netherlands. Therefore, this paper presents the results of a survey, conducted through active, prospective pediatric surveillance. We describe the occurrence and clinical aspects of ACA in the Netherlands in 2002 and 2003. Preceding infections were established with special focus on varicella. To assess underreporting and estimate the total burden of ACA in the Netherlands, we compared hospitalized cases of the pediatric surveillance with national hospitalization data using capture–recapture method for two sources. Furthermore a possible association with vaccinations was investigated.

Section snippets

Identification of patients with ACA

Patients with ACA in the study period 2002–2003 (24 months) were identified from three sources:

  • 1.

    The Netherlands Pediatric Surveillance Unit (NSCK):

This system is an active, prospective surveillance among pediatricians, reporting monthly whether they have seen a patient in hospital with a disease included in the system for that period. Purpose is a better understanding of rare and/or new disorders in childhood. There is national coverage and the response varies between 83% and 92%. For the

Patient characteristics

In 2002 and 2003, NSCK reported 55 children. Four reports were duplicates and seven children did not meet the inclusion criteria for ACA. In the same period, RIVM received eight reports of possible ACA through the safety surveillance system. Only two of these met the inclusion criteria for ACA and one of them was identical to a NSCK-report. Consequently, 45 children with ACA were included. Additional information was obtained for 43 cases through the questionnaire, discharge letter and

Discussion

This study gives an overview of the incidence rate of acute cerebellar ataxia in the Netherlands. The syndrome has a peak incidence between 2 and 4 years and boys were more often affected than girls. The clinical picture is usually mild with sometimes (8%) mild sequelae. We found no association with vaccination.

According to the CRC-estimation the incidence rate of hospitalized ACA for the Netherlands was 0.7:100,000 per year for children under 15 years of age. This is in line with other

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