HHV-6-Associated Neurological Disease in Children: Epidemiologic, Clinical, Diagnostic, and Treatment Considerations

Eliassen, Eva; Hemond, Christopher C.; Santoro, Jonathan D.

doi:10.1016/j.pediatrneurol.2019.10.004

Cited by 24 publications

(39 citation statements)

References 142 publications

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“…7,9,10 Persons with MS have an increased serological response to a selected antigen from HHV-6A, but not from HHV-6B, and this increase was also seen in serum collected before the MS diagnosis and thus it confers a risk factor for MS. 11 In addition, HHV-6A and HHV-6B are implicated in a number of other neurological diseases which commonly present with seizures or encephalitis, including HHV-6 post-transplant acute limbic encephalitis (HHV-6 PALE), Rasmussen encephalitis and febrile seizures in children. 12 It is important to consider these complications of HHV-6 infection in patients treated with immunomodulatory drugs due to their associated risk of treatment-related opportunistic infections. 13 This review will, however, only explore the role of HHV-6A and HHV-6B specifically in epilepsy and MS, the evidence to date and the future directions of this field.…”

Section: Introductionmentioning

confidence: 99%

The role of herpesvirus 6A and 6B in multiple sclerosis and epilepsy

2020

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Section: Introductionmentioning

confidence: 99%

The role of herpesvirus 6A and 6B in multiple sclerosis and epilepsy

2020

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“…Among the five patients diagnosed with meningoencephalitis or meningitis, WBC pleocytosis was present in only one patient (patient 8). This finding is not too surprising, as pleocytosis is often absent or minimal during primary infection-associated HHV-6 encephalitis (37). Thus, CSF parameters should not be used to rule out HHV-6 CNS infections in pediatric patients.…”

Section: Discussionmentioning

confidence: 98%

Pathogen or Bystander: Clinical Significance of Detecting Human Herpesvirus 6 in Pediatric Cerebrospinal Fluid

et al. 2020

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Human herpesvirus 6 (HHV-6) is an important cause of meningitis and meningoencephalitis. As testing for HHV-6 in cerebrospinal fluid (CSF) is more readily available using the FilmArray Meningitis/Encephalitis panel (FA-ME; BioFire Diagnostics, Salt Lake City, UT), we aimed to determine the clinical significance of detecting HHV-6 in order to identify true infections and to ensure appropriate antiviral initiation. Chart review on 25 patients positive for HHV-6 by FA-ME was performed to determine clinical presentation, comorbidity, treatment, and outcome. The presence of chromosomally integrated HHV-6 (ciHHV-6) DNA was also investigated. Of 1,005 children tested by FA-ME, HHV-6 was detected in 25 (2.5%). Five patients were diagnosed with either HHV-6 meningitis or meningoencephalitis based on HHV-6 detection in CSF, clinical presentation, and radiographic findings. Detection of HHV-6 by FA-ME led to discontinuation of acyclovir within 12.0 h in all 12 patients empirically treated with acyclovir. Six of the 12 patients were started on ganciclovir therapy within 6.8 h; 4 of these were treated specifically for HHV-6 infection, whereas therapy was discontinued in the remaining 2 patients. CSF parameters were not generally predictive of HHV-6 positivity. The presence of ciHHV-6 was confirmed in 3 of 18 patients who could be tested. Five of the 25 patients included in the study were diagnosed with HHV-6 meningitis/meningoencephalitis. FA-ME results led to discontinuation of empirical antiviral treatment in 12 patients and appropriate initiation of ganciclovir in 4 patients. In our institution, detection of HHV-6 using FA-ME led to faster establishment of disease etiology and optimization of antimicrobial therapy.

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“…The gold-standard method of identifying HHV-6 encephalitis is quantitative PCR in cerebrospinal fluid [ 18 ], which was not performed in our case because of the primary hypothesis of central nervous system involvement in HUS. Clinical features compatible with severe primary HHV-6 infection included a rash 3 days before the clinical manifestations of HUS, dynamic viral replication in the blood, age less than 3 years, and compatible neurological clinical symptoms and neuroimaging characteristics [ 19 ]. HHV-6 infection was likely the main cause of her neurological impairment and the poor outcome.…”

Section: Discussionmentioning

confidence: 99%

Hemolytic uremic syndrome related to Shiga-like toxin-producing Escherichia coli with encephalitis hiding a human herpesvirus-6 infection: a case report

et al. 2021

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Background Cardiac and neurological involvement in hemolytic uremic syndrome are life-threatening complications. The most frequent complications of cardiac involvement in hemolytic uremic syndrome are myocarditis and cardiac dysfunction due to fluid overload. Pericarditis remains very rare in hemolytic uremic syndrome. To our knowledge, only five cases of cardiac tamponade associated with hemolytic uremic syndrome have been described in literature. Case summary A 27-month-old Caucasian girl presented with symptoms of nonbloody diarrhea and tonic-clonic seizures. The diagnosis of Shiga-like toxin-producing Escherichia coli hemolytic uremic syndrome with central nervous system involvement was made, and stool examination revealed infection with a Shiga-like toxin-producing Escherichia coli. She did not need renal replacement therapy but had severe neurological impairment. The patient’s course was complicated by pericardial effusion. A pericardiocentesis was performed via an apical approach because the pericardial effusion was predominantly surrounding the left ventricle. Effusion analysis showed an exudate and positivity for human herpesvirus-6B on polymerase chain reaction with viremia. This finding was consistent with primary human herpesvirus-6 infection with encephalitis. Conclusion We report this uncommon case of Shiga-like toxin-producing Escherichia coli hemolytic uremic syndrome associated with a severe human herpesvirus-6 infection. Secondary isolated pericardial effusion and atypical neurological involvement are uncommon in Shiga-like toxin-producing Escherichia coli hemolytic uremic syndrome and should lead the physician to perform additional investigations.

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HHV-6-Associated Neurological Disease in Children: Epidemiologic, Clinical, Diagnostic, and Treatment Considerations

Cited by 24 publications

References 142 publications

The role of herpesvirus 6A and 6B in multiple sclerosis and epilepsy

The role of herpesvirus 6A and 6B in multiple sclerosis and epilepsy

Pathogen or Bystander: Clinical Significance of Detecting Human Herpesvirus 6 in Pediatric Cerebrospinal Fluid

Hemolytic uremic syndrome related to Shiga-like toxin-producing Escherichia coli with encephalitis hiding a human herpesvirus-6 infection: a case report

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