Cryptococcus albidus (Naganishia albida) meningitis in a young patient with T-cell acute lymphoblastic leukaemia

Herpes simplex virus (HSV) encephalitis is associated with a high risk of mortality and sequelae, and early diagnosis and treatment in the emergency department are necessary. However, most patients present with non-specific febrile, acute neurologic impairment; this may lead clinicians to overlook the diagnosis of HSV encephalitis. We aimed to identify which data collected in the first hours in a medical setting were associated with the diagnosis of HSV encephalitis. We conducted a multicenter retrospective case-control study in four French public hospitals from 2007 to 2013. The cases were the adult patients who received a confirmed diagnosis of HSV encephalitis. The controls were all the patients who attended the emergency department of Grenoble hospital with a febrile acute neurologic impairment, without HSV detection by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF), in 2012 and 2013. A multivariable logistic model was elaborated to estimate factors significantly associated with HSV encephalitis. Finally, an HSV probability score was derived from the logistic model. We identified 36 cases and 103 controls. Factors independently associated with HSV encephalitis were the absence of past neurological history (odds ratio [OR] 6.25 [95 % confidence interval (CI): 2.22-16.7]), the occurrence of seizure (OR 8.09 [95 % CI: 2.73-23.94]), a systolic blood pressure ≥140mmHg (OR 5.11 [95 % CI: 1.77-14.77]), and a C-reactive protein <10mg/L (OR 9.27 [95 % CI: 2.98-28.88]). An HSV probability score was calculated summing the value attributed to each independent factor. HSV encephalitis diagnosis may benefit from the use of this score based upon some easily accessible data. However, diagnostic evocation and probabilistic treatment must remain the rule.

Research during the past 30 years has transformed our approach to the diagnosis and management of neonatal herpes simplex virus (HSV) encephalitis.1 Nevertheless, early diagnosis of HSV encephalitis and its long-term management continue to challenge practitioners, primarily because of the paucity of clinical symptoms and laboratory abnormalities associated with early disease.1–5 Fonseca-Aten et al,6 in this issue of Pediatrics , report on an infant who developed symptomatic HSV encephalitis during administration of daily oral acyclovir (ACV) given to “suppress” HSV disease. Elements of this case spotlight issues peculiar to HSV that may assist pediatric practitioners in the timely diagnosis and effective management of neonatal HSV encephalitis.1,5,7–10 Neonatal HSV infections are often categorized into 1 of 3 syndromes: skin-eye-mouth, disseminated, and central nervous system (CNS). However, these disease patterns are not discreet, with encephalitis often due to the extension of skin-eye-mouth or disseminated disease. HSV encephalitis affects the brain cortex or, less commonly, the brainstem.1 HSV replication in the cortex of infants can be clinically unapparent,1–5 because cortical function is not required for most activities of infants. HSV CNS infection can be difficult to diagnose by examination of cerebral spinal fluid (CSF), because the meninges may not be significantly inflamed. This is particularly true in the early phases of the illness, during which treatment can have the most impact on reducing long-term neurologic morbidity.1,5,7 Also problematic is that reactivation of HSV in the CNS, which is lytic to the brain parenchyma, may be asymptomatic in infants, with neurologic impairment becoming apparent by 6 to 12 months of age.1,11 The infant reported by Fonseca-Aten et al6 was first diagnosed with encephalitis after seizures at 3 months of … Address correspondence to Lisa M. Frenkel, MD, Departments of Pediatrics and Laboratory Medicine, University of Washington and Children’s Hospital, 307 Westlake Ave N, Suite 300, Room 330, Seattle, WA 98109. E-mail: lfrenkel{at}u.washington.edu

Herpes simplex virus (HSV) encephalitis is an uncommon, but potentially devastating brain infection with significant morbidity and mortality. Some patients develop a brainstem herniation syndrome because the virus has a predilection for the temporal lobes despite prompt treatment with the antiviral drug aciclovir. We report a case of HSV encephalitis in an adolescent who developed severe cerebral oedema and subfalcine herniation which was refractory to medical management. He underwent a decompressive craniectomy with partial right temporal lobectomy. He made a rapid recovery with no physical deficits though he has some residual neuropsychological problems similar to those reported following HSV encephalitis previously. Neurosurgical intervention appears to be uncommon in HSV encephalitis: to our knowledge only four other children are reported to have had a similar procedure. We describe our case in detail and provide a full review of the literature surrounding neurosurgical intervention in severe HSV encephalitis.

We present a case of cerebral venous sinus thrombosis (CVST) as a rare complication of herpes simplex virus (HSV) encephalitis. A young man with no pertinent medical history was diagnosed...

Acyclovir (aciclovir) is a nucleoside analogue antiviral drug related to cytarabine, idoxuridine, trifluridine and vidarabine. In common with these earlier antivirals, acyclovir is active against some members of the herpesvirus group of DNA viruses. The efficacy of topical acyclovir has been convincingly demonstrated in ocular herpetic keratitis, and in initial and primary initial genital herpes infection, but little or no clinical benefit was seen when non-primary initial genital infections were assessed separately. Acyclovir ointment demonstrated little benefit in recurrent genital herpes but topical acyclovir cream decreased the course of the infection by 1 to 2 days. Orally and intravenously administered acyclovir were beneficial in initial genital herpes infections, and oral therapy shortened the duration of recurrent infections by 1 to 2 days but did not ameliorate pain. In non-immunocompromised patients with recurrent herpes simplex labialis, generally little clinical benefit was seen with the use of topical acyclovir ointment even when therapy was initiated during the prodromal phase, while topical acyclovir cream effected small but significant improvements in the clinical but not the symptomological course of the disease. However, in immunocompromised patients, both intravenous and topical acyclovir shortened the clinical course of herpes simplex virus infections occurring mainly on the lips, oral mucosa and face, and prophylaxis with either oral or intravenous acyclovir suppressed the appearance of recurrent lesions from latent virus for the period of drug administration, but acyclovir did not eradicate latent herpesviruses. In non-immunocompromised patients, intravenous acyclovir was shown to decrease the acute pain of zoster, especially in the elderly, but postherpetic neuralgia was not ameliorated. When immunocompromised patients were studied, intravenous acyclovir inhibited the progression of zoster infections and shortened the healing time and duration of viral shedding in patients with cutaneous disseminated zoster. However, acute and post-herpetic pain were not significantly affected. Well designed controlled studies are underway to establish the efficacy of acyclovir in herpes simplex encephalitis and cytomegalovirus infections in immunocompromised patients, infections due to Epstein-Barr virus, and neonatal herpesvirus infections. Despite some aspects of the drug's use which require further clarification, acyclovir will make a major impact on the treatment of herpesviral infections. Barring unexpected findings with wider clinical use, it will become the agent of choice in several conditions.

Newborns are more susceptible to severe disease from infection than adults, with maturation of immune responses implicated as a major factor. The type I interferon response delays mortality and limits viral replication in adult mice in a model of herpes simplex virus (HSV) encephalitis. We found that intact type I interferon signaling did not control HSV disease in the neonatal brain. However, the multifunctional HSV protein γ34.5 involved in countering type I interferon responses was important for virulence in the brain in both age groups. To investigate this observation further, we studied a specific function of γ34.5 which contributes to HSV pathogenesis in the adult brain, inhibition of the cellular process of autophagy. Surprisingly, we found that the beclin binding domain of γ34.5 responsible for inhibiting autophagy was dispensable for HSV disease in the neonatal brain, as infection of newborns with the deletion mutant decreased time to mortality compared to the rescue virus. Additionally, a functional beclin binding domain in HSV γ34.5 did not effectively inhibit autophagy in the neonate, unlike in the adult. Type I IFN responses promote autophagy in adult, a finding we confirmed in the adult brain after HSV infection; however, in the newborn brain we observed that autophagy was activated through a type I IFN-independent mechanism. Furthermore, autophagy in the wild-type neonatal mouse was associated with increased apoptosis in infected regions of the brain. Observations in the mouse model were consistent with those in a human case of neonatal HSV encephalitis. Our findings reveal age-dependent differences in autophagy for protection from HSV encephalitis, indicating developmental differences in induction and regulation of this innate defense mechanism after HSV infection in the neonatal brain.

Patient: Male, 49-year-old Final Diagnosis: Neurosyphilis Symptoms: Behavioral disturbance • confusion • disorientation • hallucinations • memory loss Medication: Penicillin G • acyclovir Clinical Procedure: Lumbar puncture Specialty: Infectious Diseases • Neurology • Radiology Objective: Rare disease Background:Neurosyphilis is a central nervous system infection caused by Treponema pallidum, that can develop at any time after the initial infection. The clinical signs of neurosyphilis are very variable, as well as its radiological features, and it is a diagnostic challenge. Knowledge of clinical symptoms and correct laboratory diagnostics, combined with routine radiological examination and additional diagnostic tools, such as high-resolution, three-dimensional FLAIR sequence, T2-weighted, and T1-weighted contrast-enhanced magnetic resonance imaging (MRI) are key to making an accurate diagnosis of neurosyphilis.Case Report:We present the clinical case of a patient who presented a 1-year history of vague clinical symptoms and was misdiagnosed with herpes simplex virus (HSV) encephalitis. Initial head MRI revealed extensive cerebral white matter lesions with cortical contrast enhancement, mainly of anterior and medial parts of the left temporal lobe, as typically seen in HSV encephalitis. Empirical therapy with acyclovir was started until a diagnosis of syphilis was confirmed with laboratory findings. Later, the therapy was changed to penicillin G. The patient’s condition improved after receiving targeted treatment. A control MRI scan was performed, and previously detected changes in the brain had decreased significantly.Conclusions:MRI is the imaging of choice to support the diagnosis of neurosyphilis. Our findings suggest that neuroimaging can play an important role in indicating suspicion of syphilitic encephalitis. Enhancement of the anterior and medial parts of the temporal lobe is an atypical imaging finding, and it can simulate an infection with HSV. Early treatment is critical to a positive outcome.

64-Year-Old Man With Subacute Altered Mental Status and Headache

Herpes Simplex Virus (HSV) encephalitis and Herpes Zoster skin lesions are both caused by different strains of the herpes virus. Herpes Simplex Virus (HSV) encephalitis is caused by the Herpes Simplex Virus (HSV), typically HSV-1, while Herpes Zoster, commonly known as shingles, is caused by the Varicella-Zoster Virus (VZV), which is also a member of the herpesvirus family. This is a case report of HSVE with HZ in a 65 year’s old male patient admitted to hospital with chief complaints of erythematous fluid filled rash over abdomen since 1 week, two episodes of generalised type seizures involved all four limbs and with altered sensorium since 1 day. His past medical history revealed that he was a known case of pulmonary tuberculosis (PTB) 2 years ago and taken antitubercular therapy (ATT) for 6 months and also he had developed chickenpox in his childhood. The patient was diagnosed with herpes skin lesion and herpes simplex virus encephalitis based on his USG report and clinical, neurological symptoms respectively. His laboratory tests revealed abnormal haematology and LFT parameters, USG abdomen showed grade 1 fatty changes with hepatomegaly, echogenic sediments in urinary bladder and herpes zoster eruption in dermatomal distribution, chest X-ray showed suggestive sequalae of pulmonary Koch’s. the treatment was initiated with Acyclovir, Levetiracetam, Tramadol, etc.

Patients with herpes simplex virus (HSV) encephalitis (HSE) often develop neuronal autoantibody-associated encephalitis (AE) post-infection. Risk factors of AE are unknown. We tested the hypotheses that predisposition for AE post-HSE may be involved, including genetic variants at specific loci, human leucocyte (HLA) haplotypes, or the blood innate immune response against HSV, including type I interferon (IFN) immunity. Patients of all ages with HSE diagnosed between 1 January 2014 and 31 December 2021 were included in one of two cohorts depending on whether the recruitment was at HSE onset (Spanish Cohort A) or by the time of new neurological manifestations (international Cohort B). Patients were assessed for the type of neurological syndromes; HLA haplotypes; blood type I-IFN signature [RNA quantification of 6 or 28 IFN-response genes (IRG)] and toll-like receptor (TLR3)-type I IFN-related gene mutations. Overall, 190 patients (52% male) were recruited, 93 in Cohort A and 97 in Cohort B. Thirty-nine (42%) patients from Cohort A developed neuronal autoantibodies, and 21 (54%) of them developed AE. Three syndromes (choreoathetosis, anti-NMDAR-like encephalitis and behavioural-psychiatric) showed a high (≥95% cases) association with neuronal autoantibodies. Patients who developed AE post-HSE were less likely to carry the allele HLA-A*02 (4/21, 19%) than those who did not develop AE (42/65, 65%, P = 0.0003) or the Spanish general population (2005/4335, 46%, P = 0.0145). Blood IFN signatures using 6 or 28 IRG were positive in 19/21 (91%) and 18/21 (86%) patients at HSE onset, and rapidly decreased during follow-up. At Day 21 after HSE onset, patients who later developed AE had higher median IFN signature compared with those who did not develop AE [median Zs-6-IRG 1.4 (0.6; 2.0) versus 0.2 (-0.4; 0.8), P = 0.03]. However, a very high median Zs-6-IRG (>4) or persistently increased IFN signature associated with uncontrolled viral infection. Whole exome sequencing showed that the percentage of TLR3-IFN-related mutations in patients who developed AE was not different from those who did not develop AE [3/37 (8%) versus 2/57 (4%), P = 0.379]. Multivariate logistic regression showed that a moderate increase of the blood IFN signature at Day 21 (median Zs-6-IRG >1.5 but <4) was the most important predictor of AE post-HSE [odds ratio 34.8, interquartile ratio (1.7-691.9)]. Altogether, these findings show that most AE post-HSE manifest with three distinct syndromes, and HLA-A*02, but not TLR3-IFN-related mutations, confer protection from developing AE. In addition to neuronal autoantibodies, the blood IFN signature in the context of HSE may be potentially useful for the diagnosis and monitoring of HSE complications.

Herpes simplex virus (HSV) encephalitis is the most common cause of sporadic fatal encephalitis worldwide, and central nervous system (CNS) involvement is observed in approximately one-third of neonatal HSV infections . In recent years, single-gene inborn errors of innate immunity have been shown to be associated with susceptibility to HSV encephalitis . Temporal lobe abnormalities revealed by magnetic resonance imaging-the most sensitive imaging method for HSV encephalitis-are considered strong evidence for the disease. Detection of HSV DNA in the cerebrospinal fluid by polymerase chain reaction (PCR) is the gold standard for the diagnosis of HSV encephalitis and neonatal meningoencephalitis. Intravenous acyclovir for 14-21 days is the standard treatment in HSV encephalitis. Neurological outcomes in neonates are improved by intravenous high-dose acyclovir for 21days followed by oral acyclovir suppressive therapy for 6months. Varicella-zoster virus (VZV) causes a wide range of CNS manifestations. VZV encephalitis typically occurs after primary infection, and reactivation of VZV may cause encephalitis. On the other hand, VZV infection of cerebral arteries produces vasculopathy, which can manifest as ischemic stroke. Vasculopathy can occur after primary infection or reactivation of VZV. PCR detection of VZV DNA in the cerebrospinal fluid can be used for the diagnosis of encephalitis or vasculopathy. Although there are no controlled treatment trials to assess VZV treatments of encephalitis or vasculopathy, intravenous acyclovir is a common treatment.

In January 2008, a 59-year-old man with a history of diabetes mellitus was admitted to our hospital with herpes simplex virus (HSV) encephalitis of his right temporal lobe, which was diagnosed by PCR testing of his cerebrospinal fluid (CSF). He was treated with intravenous acyclovir for three weeks and made a full recovery. On discharge, his CSF was negative for HSV on PCR testing. Seven years later, in March 2015, the man was readmitted to our hospital with fever, disorientation, and nominal dysphasia. Diffusion-weighted MRI of his head revealed a high-intensity area in his left temporal lobe. Testing of his CSF revealed a moderately increased monocyte count and HSV on PCR testing, so he was diagnosed with recurrent HSV encephalitis. He was treated with intravenous acyclovir for three weeks. On discharge, his CSF was negative for HSV on PCR testing, but he had mild residual amnesia. There have been few reports of HSV encephalitis with viral reactivation recurring after a long remission period in adults. This case illustrates the need for prolonged follow up of individuals with HSV encephalitis in order to detect recurrences.

Herpes simplex virus(HSV) encephalitis is typically an acute, monophasic illness but can rarely present as a chronic granulomatous encephalitis, especially among immunocompromised individuals. The diagnosis of chronic HSV encephalitis is challenging due to its prolonged latency period, atypical imaging findings, and potential false-negative cerebrospinal fluid (CSF) polymerase chain reaction (PCR) results. This report describes a rare case of chronic granulomatous HSV encephalitis in a child with an underlying immunodeficiency disorder- DiGeorge syndrome (DGS). A developmentally normal 10-month-old girl initially presented with fever and seizures, was diagnosed with acute encephalitis, and received intravenous acyclovir. Following the illness, she exhibited neurodevelopmental delay and gliotic changes in brain imaging. At 12 years of age, she was admitted with refractory seizures and a respiratory infection. MRI revealed new cortical lesions and CSF analysis showed mild pleocytosis with elevated proteins. Despite symptomatic management, her condition worsened, with progressive neurological decline and radiological evidence of tumefactive or granulomatous lesions. A brain biopsy was performed, revealing HSV-1 positivity on PCR and immunohistochemistry, confirming chronic HSE. Given the atypical course, genetic testing was conducted, showing a 22q11.2 microdeletion consistent with DGS. The patient was treated with intravenous acyclovir and corticosteroids, followed by long-term oral acyclovir prophylaxis. Over two years of follow-up, she showed significant clinical and radiological improvement, with seizure resolution and partial recovery of developmental milestones. This case highlights the potential for HSV to cause chronic granulomatous encephalitis, particularly among children with underlying immunodeficiency. It underscores the diagnostic challenge posed by prolonged latency and false-negative CSF PCR results and the importance of brain biopsy for definitive diagnosis. Additionally, this report suggests a potential link between DGS-related immunodeficiency and chronic HSV infection, emphasizing the need for genetic evaluation in atypical encephalitis cases. Long-term acyclovir therapy may be beneficial in such patients, although the optimal duration remains uncertain.

PP13.6 – 3003: Choreoathetotic “relapse” of HSV encephalitis

Chorea has been described as an initial sign of relapse in children with herpes simplex virus encephalitis. We describe the detection of anti-basal ganglia antibodies (ABGA) in plasma and cerebrospinal...