Relapse of Herpes Encephalitis after Acyclovir Therapy: Report of Two New Cases and Review of the Literature

Valencia, Ignacio; Miles, Daniel; Melvin, John Muil; Khurana, Divya S.; Kothare, S N; Hardison, H. Huntley; Legido, Agustín

doi:10.1055/s-2004-830372

Cited by 43 publications

(31 citation statements)

References 25 publications

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“…Overall, HSE recurrence is rare, being reported in only about 10% of affected children. 4,30,31 It may occur early (before 18 months) or late (after 18 months), reflecting different mechanisms. Late relapses of HSE are particularly rare and their underlying mechanism remains unclear.…”

Section: 26mentioning

confidence: 99%

TLR3 deficiency in herpes simplex encephalitis

Lim¹,

Seppänen²,

Hautala³

et al. 2014

Neurology

137

120

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Objective: To determine the proportion of children with herpes simplex encephalitis (HSE) displaying TLR3 deficiency, the extent of TLR3 allelic heterogeneity, and the specific clinical features of TLR3 deficiency. Methods:We determined the sequence of all exons of TLR3 in 110 of the 120 patients with HSE enrolled in our study who do not carry any of the previously described HSE-predisposing mutations of TLR3 pathway genes (TLR3, UNC93B1, TRIF, TRAF3, and TBK1). All the new mutant TLR3 alleles detected were characterized experimentally in-depth to establish the causal relationship between the genotype and phenotype.Results: In addition to the 3 previously reported TLR3-deficient patients from the same cohort, 6 other children or young adults with HSE carry 1 of 5 unique or extremely rare (minor allele frequency ,0.001) missense TLR3 alleles. Two alleles (M374T, D592N) heterozygous in 3 patients are not deleterious in vitro. The other 3 are deleterious via different mechanisms: G743D1R811I and L360P heterozygous in 2 patients are loss-of-function due to low levels of expression and lack of cleavage, respectively, and R867Q homozygous in 1 patient is hypomorphic. The 3 patients' fibroblasts display impaired TLR3 responses and enhanced herpes simplex virus 1 susceptibility. Overall, TLR3 deficiency is therefore found in 6 (5%) of the 120 patients studied. There is high allelic heterogeneity, with 3 forms of autosomal dominant partial defect by negative dominance or haploinsufficiency, and 2 forms of autosomal recessive defect with complete or partial deficiency. Finally, 4 (66%) of the 6 TLR3-deficient patients had at least 1 late relapse of HSE, whereas relapse occurred in only 12 (10%) of the total cohort of 120 patients.Conclusions: Childhood-onset HSE is due to TLR3 deficiency in a traceable fraction of patients, in particular the ones with HSE recurrence. Mutations in TLR3 and TLR3 pathway genes should be searched and experimentally studied in children with HSE, and patients with proven TLR3 deficiency should be followed carefully. TLR3 is one of the most highly conserved TLRs in humans that have evolved under the strongest purifying selection.1 TLR3 recognizes double-stranded RNA (dsRNA), a by-product produced during the viral replication of most viruses, including herpes simplex virus 1 (HSV-1).2 The most common known clinical consequence of human TLR3 deficiency is childhood herpes simplex encephalitis (HSE). Childhood HSE is a rare life-threatening complication of primary infection with HSV-1, a common neurotropic dsDNA virus that is innocuous in most children.3 HSE is the most common form of sporadic viral encephalitis in Western countries. 4,5 The pathogenesis of HSE had long remained unclear. Our recent studies have demonstrated that HSE may result from singlegene inborn errors of TLR3-mediated immunity in some children, 6 with homozygous or

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Section: 26mentioning

confidence: 99%

TLR3 deficiency in herpes simplex encephalitis

Lim¹,

Seppänen²,

Hautala³

et al. 2014

Neurology

137

120

View full text Add to dashboard Cite

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“…Herpes simplex encephalitis · Recurrence · Autoimmune reaction [4,16]. Die Inzidenz früher Rezidive wird bei Kindern weitaus häufiger beschrieben als bei Erwachsen, die Häufigkeit in epidemiologischen Erhebungen schwankt zwischen 11-26% [3,4].…”

Section: Introductionunclassified

“…Das Risiko einer Reaktivierung ist nicht einschätz-bar. Sehr junge Kinder scheinen ein hö-heres Risiko für eine rekurrierende Enzephalitis zu tragen [16]. Durch eine erneute Aciclovir-Therapie kann auch bei Nachweis einer Virusreplikation nicht immer eine Besserung erzielt werden.…”

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“…Ein Frührezidiv manifestiert sich innerhalb von 2-4 Wochen nach Ersterkrankung mit unterschiedlichen neurologischen Symptomen und Fieber. Die Prognose ist schlecht: 13% der Fälle versterben, 81% entwickeln eine deutliche neurologische Schädigung [16]. Die Unterscheidung zwischen Autoimmunreaktion und echter Virusaktivierung ist klinisch oft unklar, in einigen Fällen sind beide Pathomechanismen zu vermuten.…”

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Reaktivierung nach einer Herpes-simplex-Enzephalitis

Vieker

Remmel-Spornhauer²,

Boksch³

et al. 2007

Monatsschr Kinderheilkd

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“…74 Shorter duration of treatment is associated with occasional relapse with acyclovir-sensitive HSV. 75 There is insufficient evidence to support valacyclovir as an equally effective agent to date.…”

Section: Immunocompromisedmentioning

confidence: 99%

Antiviral selection in the management of acute retinal necrosis

Tam

Hooper²,

Lightman

2009

OPTH

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Abstract:There is no consensus on the optimal antiviral regimen in the management of acute retinal necrosis, a disease caused by herpetic viruses with devastating consequences for the eye. The current gold standard is based on retrospective case series. Because the incidence of disease is low, few well-designed, randomized trials have evaluated treatment dosage and duration. Newer oral antiviral agents are emerging as alternatives to high-dose intravenous acyclovir, avoiding the need for inpatient intravenous treatment. Drug resistance is uncommon but may also be difficult to identify. Antiviral drugs have few side effects, but special attention needs to be paid to patients who have underlying renal disease, are pregnant or are immunocompromised.

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Relapse of Herpes Encephalitis after Acyclovir Therapy: Report of Two New Cases and Review of the Literature

Cited by 43 publications

References 25 publications

TLR3 deficiency in herpes simplex encephalitis

TLR3 deficiency in herpes simplex encephalitis

Reaktivierung nach einer Herpes-simplex-Enzephalitis

Antiviral selection in the management of acute retinal necrosis

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