Acute disseminated encephalomyelitis secondary to serogroup B meningococcal vaccine

Acute disseminated encephalomyelitis secondary to serogroup B meningococcal vaccine

Journal of the Neurological Sciences 370 (2016) 53–54 Contents lists available at ScienceDirect Journal of the Neurological Sciences journal homepag...

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Journal of the Neurological Sciences 370 (2016) 53–54

Contents lists available at ScienceDirect

Journal of the Neurological Sciences journal homepage:

Letter to the Editor Acute disseminated encephalomyelitis secondary to serogroup B meningococcal vaccine

(Fig. 1D). Six months later, the patient remained asymptomatic. At present, the monophasic course of the disease and the patient's good clinical and radiological progress support the diagnosis of post-vaccinal ADEM.

2. Discussion Dear Editor, Acute disseminated encephalomyelitis (ADEM) is a monophasic disease that presents primarily in children and adolescents following an infection or immunization [1]. It is considered an immune-mediated condition and it predominantly affects the white matter of the brain and spinal cord [1]. The incidence in the adult population has not been precisely established; it is estimated that b5% of all cases arise after antigenic vaccination [2]. The vaccines most frequently linked to this disease are MMR (measles, mumps, and rubella), influenza, rabies, and tetanus [3]. This letter provides a novel description of ADEM secondary to delivery of a serogroup B meningococcal vaccine.

1. Case presentation We present the case of a 55-year-old woman, an administrative assistant at our hospital with no relevant medical history. She reported a tingling sensation in the area of her left calf beginning a few hours after she received a serogroup B meningococcal vaccine. In 24 h, the sensory level had reached the groin, and at 5 days, it had risen to the left mammary region. A neurological examination detected left tactile hypoesthesia with hypalgesia at the C5 level (sensitivity to vibration, position, and pressure were also affected). Muscle balance was preserved. Tested reflexes were hyperactive without clonus. Cervicothoracic spinal MRI revealed a spindle-shaped spinal lesion, hyperintense on T2-weighted images, extending from C7 to T2 (Fig. 1C). Cerebral MR images displayed isolated bilateral frontal subcortical lesions and another precentral cortical lesion on the right side. These lesions were hyperintense in T2- and FLAIR-weighted sequences and showed no contrast enhancement (Fig. 1A and B). An emergency cytobiochemical study of the cerebrospinal fluid (CSF) yielded normal results except for mild pleocytosis (7 leukocytes). Microbiological, serological, and PCR (polymerase chain reaction) testing for neurotropic viruses in the CSF showed negative results. Evaluating oligoclonal Ig bands yielded a mirror pattern (identical bands in serum and in CSF). The IgG index was normal and serum tests for antiaquaporin-4 antibodies (anti-AQP4 or NMO-IgG) were also negative. Blood tests for autoimmune disorders, levels of angiotensin-converting enzyme (ACE), thrombophilia, and serology studies revealed no relevant changes. Since functional impairment was mild and the symptoms soon began remitting spontaneously, we opted for watchful waiting. A new neuroimaging study was performed 4 months later; the brain MRI scan showed that the supratentorial lesions described above were still visible but appeared to be healing, whereas the spinal lesion had disappeared 0022-510X/© 2016 Elsevier B.V. All rights reserved.

Neurological complications associated with vaccines are quite rare [2]. At present, the term ADEM refers to a monophasic inflammatory demyelinating process that affects the central nervous system (CNS) and tends to follow infection or vaccination. Although the pathophysiology of this disease is unknown, the most widely-accepted hypothesis states that the inflammatory components and the secondary autoimmune response are interrelated pathogenic events [3]. Available evidence suggests that there is a temporary autoimmune response that targets myelin as a result of cross-reactivity due to molecular mimicry of viral and self-peptides [3,4]. Another hypothesis posits that the infectious agent provokes non-specific clonal activation of autoreactive T cells. These autoantibodies or autoreactive T cells might be able to cross the blood-brain barrier and favor activation of other lymphocytes and macrophages, which in turn would elicit inflammation and demyelination in the CNS [3,4]. One current theory is that an underlying genetic basis would allow the original infectious agent to trigger this abnormal immune response in susceptible or predisposed individuals [5]. The appearance of ADEM is most commonly associated with infection with measles, followed by varicella-zoster and rubella. Other associated non-viral or bacterial agents include Borrelia, Mycoplasma pneumoniae, β-hemolytic Streptococcus, and gastrointestinal Campylobacter [3]. Among cases associated with immunizations, the vaccines most commonly implicated are measles, influenza, rubella, mumps, whooping cough, and hepatitis B [3]. There is only one published case of ADEM associated with serogroup A and C meningococcal vaccine [6]. Invasive meningococcal disease (IMD), which has 2 main forms of presentation (sepsis and meningitis), is a serious and potentially deadly disease and therefore a major healthcare concern. The B serogroup is predominant in Spain and the rest of Europe, and incidence of the disease is estimated at 0.77/ 100,000 person-years according to the European Centre for Disease Prevention and Control data from 2011 [7]. Two vaccines against serogroup B meningococcus have been approved by the Food and Drug Administration (FDA): the first (MenBFHbp [Trumenba®, Wyeth Pharmaceuticals, Inc.]) was authorized in 2014 and the second (MenB-4C [Bexsero®, Novartis Vaccines]) has been available since 2015 [8,9]. Bexsero® is a recombinant tetra-antigen vaccine designed using a novel technique known as reverse vaccinology. It contains three subcapsular antigens to meningococcus group B (Neisserial adhesion protein or NadA, factor H binding protein or fHbp, and Neisseria Heparin Binding Antigen or NHBA) combined with outer membrane vesicles (OMV) from the strain of Neisseria meningitidis NZ 98/254 that expresses serosubtype 1.4 of outer membrane protein porin A (PorA) [10]. The safety of this vaccine has been


Letter to the Editor

course of the disease confirmed the diagnosis. As far as we know, this is the first published case of ADEM after immunization with MenB-4C. Statement of ethics The authors have no ethical conflicts to declare. Disclosure statement The authors declare that there are no conflicts of interest and that no funding was received for this report. References

Fig. 1. Axial FLAIR MR images taken at time of admission (A and B) and sagittal T2weighted cervicothoracic MR images at admission (C) and follow-up image (D). Bilateral frontal subcortical lesions, right frontal precentral cortical lesions (A and B) and spinal myelitic lesion extending from C7 to T2 (measuring 3 × 3 × 34 mm on its anterior-posterior, transverse and craniocaudal axes respectively) (C). Follow-up study of spinal cord (same sequence) taken 4 months after symptom onset and showing marked improvement of the lesion (D).

analyzed in 10 clinical trials including 5.849 infants and children under the age of 2, and 2.677 adolescents and adults aged 11 to 55 [10]. Furthermore, a total of 59.091 subjects have received at least one dose of MenB-4C in different vaccination campaigns [9]. The most frequently observed local and systemic reactions were pain at the injection site (≥83%), non-specific myalgias (≥48%), and headache (≥33%) [9]. Severe adverse events (anaphylaxis, rhabdomyolysis) that may be related to the vaccine have been reported occasionally [9]. Nevertheless, although the vaccine is considered safe for all age groups, constant pharmacovigilance is of the utmost importance. Our patient developed clinical symptoms compatible with ADEM, with demyelinating lesions in the subcortical white matter and spinal cord, after her initial vaccination with Bexsero®. The clinical and radiological

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Sira Carrasco García de León Ph.D.⁎ Department of Neurology, University General Hospital of Ciudad Real Obispo Rafael Torija S/N, Ciudad Real, Spain Corresponding author. José Manuel Flores Barragán Ph.D. C/Obispo Rafael Torija, Ciudad Real, Spain 25 August 2016 Available online 13 September 2016