An Autopsy Case of Varicella Zoster Virus Encephalitis with Multiple Brain Lesions.

Varicella-zoster virus (VZV) encephalitis in the absence of vasculopathy may rarely occur in association with herpes zoster. We herein report the case of a 67-year-old woman with non-Hodgkin's lymphoma undergoing chemotherapy who presented with an acute alteration in consciousness. Magnetic resonance imaging of the brain revealed multiple and nonspecific lesions of hyperintensity with mild edema in the cortex and subcortex. She was treated with intravenous acyclovir. However, two days after admission, the patient died and was diagnosed with VZV encephalitis. This case highlights the risk of VZV reactivation with severe neurological complications in patients undergoing immunosuppressive therapy.

[An autopsied case of severe varicella zoster virus-associated encephalomyelitis under immunosuppressant therapy].

The patient was a 40-year-old woman who was previously diagnosed with systemic lupus erythematosus and myasthenia gravis and had received prednisolone and tacrolimus for more than 7 years. In February 2017, she noticed pain in her lower back and weakness of the lower limbs, and was referred to our hospital on day 5. She had shingles in the right lower thoracic dermatomes and Brown-Séquard syndrome with right-sided dominant weakness in her lower limbs and left-sided superficial sensory disturbance below the L1 level. Varicella zoster virus (VZV)-associated myelopathy was suspected because of her symptoms and clinical findings. Despite the immediate administration of intravenous acyclovir after hospitalization, she lost consciousness and experienced a seizure related to cerebral hemorrhage in the left temporal lobe on the night of day 5. MRI showed enhanced lesions along the spinal cord and leptomeninges of the brainstem and temporal lobe. VZV-IgG and VZV-DNA were positive in the cerebrospinal fluid. Based on these clinical features and laboratory findings, she was diagnosed as VZV-associated vasculopathy and myelopathy. She subsequently had multiple cerebral infractions and hemorrhage, and developed sudden cardiopulmonary arrest on day 6, culminating in death on day 17. Autopsy showed that inflammatory mononuclear cells had infiltrated the vascular walls of the spinal cord. Immunohistochemistry revealed that some neurons and macrophages in the white matter of the spinal cord were positive for VZV. In addition, atrophic neurons, satellite cells surrounding these neurons, and infiltrating macrophages were immune-positive for VZV at the L2 dorsal root ganglia. These findings were consistent with VZV-associated vasculopathy and myelitis. Under immunosuppressive conditions, VZV can cause shingles and neuronal complications such as vasculopathy and myelitis, which are sometimes fatal despite the immediate administration of intravenous acyclovir. New treatment drugs or drugs to prevent VZV activation are desired.

Varicella zoster virus encephalitis in solid organ transplant recipients: Case series and review of literature.

Herpes zoster encephalitis (HZE) is a rare complication of varicella zoster virus (VZV) infection. We report two cases of HZE in solid organ transplant (SOT) recipients and review 10 other cases in the literature. In this review, rash was present in 67% of cases. Despite the absence of a rash, high clinical suspicion for HZE is necessary and empiric antiviral therapy should be considered. While with variable outcome, it was associated with high mortality rate of 42%. Prompt initiation of antiviral therapy remains crucial in decreasing morbidity and mortality from this fatal disease.

Recurrent Herpes Simplex Virus Encephalitis After Neurologic Surgery.

BACKGROUND: The herpes simplex virus (HSV) is the most common cause of sporadic encephalitis worldwide. Even with proper treatment, this infection is associated with a mortality rate of 19%-30% and with potential neurologic sequelae. Recurrences of encephalitis are rare and limited to a few cases in the literature. Although the mechanism of reactivation has not yet been clarified, in our patient, the surgery might have acted as a precipitating factor. CASE DESCRIPTION: The case involved a female 10-year-old patient with a history of type 1 HSV encephalitis since 24 months of age. Secondarily, the patient developed postherpetic epilepsy in the following years. At 10 years old, she was referred to the epilepsy surgery service, and an elective right temporal lobectomy was performed. After surgery, the patient experienced severe clinical deterioration characterized by fever, severe headache, and altered state of consciousness. Encephalitis was diagnosed based on a positive polymerase chain reaction for HSV in the cerebrospinal fluid. The symptoms remitted after 8 weeks of treatment with acyclovir. The histopathologic diagnosis was a chronic encephalitic process with late secondary parenchymal changes without specific viral cytopathic findings. The only limitation that persisted was related to fine movements of the left hand. One year after surgery, the patient rejoined her school activities and is currently free of seizures. CONCLUSIONS: HSV encephalitis is a rare but serious complication that should be suspected in cases of unexplained postoperative fever with altered consciousness, especially in patients with histories of encephalitic states.

Varicella zoster virus rhombencephalomyelitis following radiation therapy for oropharyngeal carcinoma.

We report a 64-year-old man with a history of stage IV oropharyngeal squamous cell carcinoma treated with cisplatin and cetuximab followed by radiation therapy who developed a rapidly advancing rhombencephalomyelitis 11 months after the completion of radiation to the base of his tongue. His initial symptoms were left ear paresthesias, dysphagia, and progressive descending weakness. Routine cerebrospinal fluid (CSF) analysis was unremarkable. Initial MRI of the brain and cervical spinal cord revealed a demarcated symmetrical heterogeneously enhancing intramedullary lesion involving the cervicomedullary spinal cord. Progressive neurological worsening included increasing weakness of his limbs, facial weakness and ocular motility disorders and MRI revealed that the lesion was advancing into his pons and cervical spinal cord. Empiric treatment for radiation myelitis was initiated. Although CSF polymerase chain reaction was negative for varicella zoster virus (VZV), antibody studies revealed intrathecal synthesis of antibody to VZV and treatment for VZV was started as well. Improvement was slow and incomplete with subsequent worsening resulting in death in 5.5 weeks. The diagnosis of rhombencephalitis and myelitis following radiation therapy may be exquisitely challenging. The possibility of VZV, a treatable disorder, should be included in the differential diagnosis.

Varicella zoster virus encephalomyelitis as a late complication following haematopoietic stem cell transplantation.

Varicella zoster virus (VZV) causes the primary infection manifesting as varicella or chickenpox, with possibility of reactivation later in life. A 71-year-old man presented with headache and lower extremity weakness. There was no evidence of skin lesions to suggest a recent zoster infection. The patient had a history of multiple myeloma diagnosed 2 years earlier, treated with chemotherapy and autologous stem cell transplant. Antimicrobial prophylaxis was discontinued 12 months after the transplant. MRI of the brain demonstrated areas of T2/fluid-attenuated inversion recovery hyperintensity in bilateral cerebral white matter and MRI of the spine demonstrated enhancement along the cauda equine. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis and VZV DNA was detected by PCR in the CSF. The patient was treated with 8 weeks of antiviral therapy with complete resolution of symptoms. VZV should be considered in patients with haematopoietic stem cell transplantation presenting with similar neurological manifestations even in the absence of dermatological signs.

Herpes zoster ophthalmicus progressing to encephalitis: beware pain preceding the rash.

We present a challenging case in which the dermatomal pain associated with herpes zoster ophthalmicus preceded the cutaneous rash by several days. It thus highlights the need to consider this diagnosis among the differentials for severe unilateral headache in the elderly. The patient unfortunately progressed to develop encephalitis, an uncommon but serious complication of zoster reactivation and a reminder that this remains an important cause of morbidity and mortality in the elderly population.

Epstein-Barr virus-related lymphoproliferative disorder, cytomegalovirus reactivation, and varicella zoster virus encephalitis during treatment of medulloblastoma.

The case of a 14-year-old girl who developed Epstein-Barr virus-related lymphoproliferative disorder, cytomegalovirus reactivation, and Varicella zoster virus encephalitis during treatment for medulloblastoma is described. The patient was diagnosed with a cerebral medulloblastoma and treated with systemic chemotherapy, intrathecal chemotherapy, and radiotherapy. Six months later, she developed persistent low-grade fever, abdominal pain, and vomiting. Several mucosal or ulcerated lesions of the stomach and colon were found on fiberscopy. The infiltrating cells were positive for CD20 and EBER1, and the diagnosis of lymphoproliferative disorder was made. CMV antigen was found in the peripheral lymphocytes at that time. At the same time, it was noted that the patient's language was inappropriate for her age, and a facial and abdominal rash, as well as a right facial palsy, had developed. She was then diagnosed as having VZV encephalitis, because VZV was detected in the CSF. She was treated subsequently with acyclovir and oral steroid, and the VZV encephalitis resolved. The lymphoproliferative disorder improved gradually with rituximab, ganciclovir, and total nutritional support. At the time of the development of the lymphoproliferative disorder and VZV encephalitis, the patient had severe lymphopenia and this may have caused these rare phenomena in a non-transplant setting.

[Acute lymphoblastic leukemia complicated with varicella zoster virus meningoencephalitis and visceral dissemination after related bone marrow transplantation].

Meningitis or encephalitis by varicella-zoster virus (VZV) after hematopoietic stem cell transplantation (HSCT) is rarely reported. We encountered a case of meningoencephalitis with VZV re-activation 18 months after related bone marrow transplantation for recurrent acute lymphoblastic leukemia. The patient had been administered steroid and cyclosporine for chronic graft-versus-host disease. A high DNA copy number of VZV, 4.9×10(7) copies was detected in the cerebrospinal fluid. VZV also caused severe pneumonia and acute renal failure soon after the onset of meningoencephalitis. The patient was successfully treated with acyclovir, although he was left with persistent neurological sequelae. Both prompt diagnosis and early treatment of VZV reactivation are important to avoid a fatal outcome.

Varicella zoster virus encephalitis during treatment with anti-tumor necrosis factor-alpha agent in a psoriatic arthritis patient.

The introduction of targeted immunotherapies has greatly improved the therapeutic options of several inflammatory diseases such as psoriatic arthritis. However treatment-related opportunistic infections and viral reactivations may still occur. We describe a case of varicella zoster virus (VZV) encephalitis due to the reactivation of latent VZV infection during a long therapy with the anti-tumor necrosis factor-alpha (TNF-alpha) drug Adalimumab. The low incidence of VZV encephalitis in patients treated with biological agents does not justify VZV serological screening in these subjects, but careful monitoring of the patients is recommended to recognize early signs and symptoms of herpes zoster to start prompt antiviral therapy to prevent associated complications.

VZV meningitis following varicella vaccine.

Live attenuated varicella zoster virus is administered to prevent varicella in children and herpes zoster in the elderly. We report a case of disseminated herpes zoster in a previously healthy elderly woman hours after Oka strain vaccination. PCR and restriction enzyme analysis revealed that symptoms were caused by wild type virus.

Varicella-zoster virus vasculopathy and central nervous system immune reconstitution inflammatory syndrome with human immunodeficiency virus infection treated with steroids.

Immune reconstitution inflammatory syndrome (IRIS) is widely recognized and rarely involves the central nervous system (CNS). Patients with acquired immunodeficiency syndrome (AIDS) are at an increased risk for developing CNS-IRIS upon initiation of highly active antiretroviral therapy (HAART). This syndrome can be fatal and requires extreme vigilance in determining if a treatable underlying opportunistic infection exists. We report here a case of varicella-zoster virus (VZV) vasculopathy and CNS-IRIS in a human immunodeficiency virus (HIV)-infected patient who required prolonged steroid treatment for clinical stabilization. There are no established treatment regimens for IRIS and the use of corticosteroids in this syndrome remains controversial. Similar to our patient, severe cases of CNS-IRIS may benefit from high-dose intravenous corticosteroid treatment followed by an oral prednisone taper.

[Acute infectious encephalitis and pathogens coming from animals]. / Uminiai infekciniai encefalitai ir gyvunines kilmes ju sukelejai.

Despite better knowledge of pathophysiology and a wider use of new molecular technologies for the diagnosis, the etiological diagnosis of acute encephalitis is not established in most cases. Incidence, prognosis, rate of this disease and severity of sequelae remain unknown. In France, according to the published data, the incidence of encephalitis is estimated to be 1.9 cases per 100 000 inhabitants in average among non-HIV patients. The etiological diagnosis is established in less than 30% of cases. The more frequent diagnosis is herpetic encephalitis in adults and encephalitis caused by Varicella zoster virus in children younger than 16 years. Despite a difficult diagnosis and the lack of specific treatment for most of these infections, the etiological diagnosis should always be deeply explored to precise the individual prognosis, to allow better management of antibiotic therapy, and to improve epidemiological knowledge. We present the recommendations established by the French Society for Infectious Diseases. First designed to suit the French epidemiology, they take in count the possible exposure of patients to different epidemiological patterns. Three levels of etiological tests are proposed, from the most common infections and those, which required an immediate treatment, to the rarest ones.

Varicella-zoster virus encephalitis in a patient undergoing unrelated cord blood transplantation for myelodysplastic syndrome-overt leukemia.

Varicella-zoster virus (VZV) infection of the central nervous system (CNS) is rare after hematopoietic stem cell transplantation (SCT). Here, we describe the first patient who developed VZV encephalitis after cord blood transplantation (CBT). A 35-year-old man with myelodysplastic syndrome-overt leukemia underwent CBT. On day +23, a neutrophil count consistently greater than 0.5 x 10(9)/L was achieved. On day +42, 1 mg/kg per day of prednisolone therapy was initiated for grade III acute graft-versus-host disease (GVHD). Then, the dose of prednisolone was slowly reduced. For exacerbation of chronic GVHD, the dose of prednisolone was again increased to 1 mg/kg per day on day +231. On day +265, localized cutaneous zoster in the left thoracic region occurred, but soon resolved after acyclovir therapy. On day +309, he suddenly developed diplopia. Subsequently, right facial palsy and hearing impairment occurred. No skin rash was observed. Magnetic resonance imaging (MRI) scans revealed multifocal abnormal high-signal intensity in the CNS. A high level of VZV DNA was detected in a cerebrospinal fluid specimen. He was diagnosed with VZV encephalitis. Acyclovir was given intravenously for 40 days. Four months after the onset, the neurologic symptoms had incompletely resolved. MRI scans showed substantial resolution but with mild residual lesions. The present report indicates that VZV should be considered as a possible causative agent in patients who develop multifocal neurologic symptoms of the CNS after SCT.

Varicella zoster virus meningitis complicating sodium stibogluconate treatment for cutaneous leishmaniasis.

Sodium stibogluconate (Pentostam(R); GlaxoSmithKline) is a pentavalent antimonial compound used in the treatment of leishmaniasis, which has an association with reactivation of varicella zoster virus (VZV). We report the first known case of an immunocompetent adult who developed VZV aseptic meningitis and dermatomal herpes zoster during treatment with sodium stibogluconate.

Fatal varicella zoster virus encephalitis in two patients following allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Reduced cellular immunocompetence following allogeneic hematopoietic stem cell transplantation (aHSCT) increases susceptibility to viral infections. Varicella zoster virus (VZV) reactivation in this setting most commonly manifests as dermatomal herpes zoster but in some cases life-threatening VZV encephalitis occurs. STUDY DESIGN/RESULTS: We describe the cases of two patients who presented with shingles 3 and 18 months, respectively, after HLA-matched peripheral blood stem cell transplantation (PBSCT). Unfortunately, in the further clinical course both patients developed fatal VZV encephalitis, despite initial high-dose intravenous therapy with acyclovir and in one case with additional VZV-immunoglobulin. CONCLUSION: These two cases suggest that rapid intervention with systemic treatment is warranted and raise the question whether initial combination therapy with intravenous acyclovir and foscarnet, VZV vaccination or long-term low-dose acyclovir are needed to improve treatment and clinical outcome in immunocompromised patients, having undergone allogeneic HSCT.

An economic evaluation of varicella vaccination in Italian adolescents.

An economic evaluation was performed to assess five varicella vaccination scenarios targeted to 11-year-old Italian adolescents. The scenarios were: "compulsory vaccination" of all adolescents, recommended vaccination of susceptible adolescents on the basis of an "anamnestic screening", a "blood test" or a combination of both ("both tests") and vaccination of adolescents in the private sector, at the parents' charge ("private vaccination"). Probabilities and unit costs were taken from published sources and experts opinion. The accuracy of the anamnestic screening (81.6% sensitivity and 87.3% specificity) was derived from a separate descriptive study among 344 Italian adolescents. The costs and benefits of each scenario were simulated using a Markov model and cost-effectiveness, budget-impact and cost-benefit analyses were conducted. Of all considered scenarios, "both tests" and "anamnestic screening" were the most appealing options with an estimated net direct cost of 5058 and 8929 per life-year gained (compared to no vaccination) versus 14,693-42,842 for the other scenarios. These two scenarios further resulted in substantial net savings for society (over 600,000 per cohort, BCR: 2.17). The need for a serological confirmation was highly dependent on the sensitivity of the anamnestic screening, which is believed to increase once such a program is launched. For practical considerations, "anamnestic screening" seems to be the most convenient option.

[Dramatic improvement of urinary retention and the left lower limb paresis with methylprednisolone in a case of regional encephalitis following varicella zoster infection].

We report a previously well 14-year-old male who developed left-sided hemiconvulsion, urinary retention and hemiplegia 1 months after varicella-zoster virus (VZV) infection. Brain T2-weighted MRI showed hyperintensity in medial fronto-parietal area including cyngulate gyrus, foot division of the motor cortex, para-central lobule and corpus callosum with right predominance, which corresponded to hyperperfusion area in SPECT study. MR angiography revealed no occlusion or narrowing of vessels. Cerebrospinal fluid (CSF) showed mononuclear pleocytosis. After methylprednisolone pulse tharapy under diagnosis of regional encephalitis, the patient recovered completely. Although polymerase chain reaction(PCR) could not detect VZV-DNA in CSF, antecedent VZV infection might be closely related to pathomechanism of the regional encephalitis. Dramatic response to steroid, rapid recovery on MRI and good prognosis supported that the underlying pathology was mainly vasogenic edema rather than cytotoxic edema.

Subdural empyema and herpes zoster syndrome (Hunt syndrome) complicating removal of third molars.

We report a case of subdural empyema and herpes zoster syndrome (Hunt syndrome) complicating routine removal of third molars. Subdural empyema is an extremely rare but life-threatening complication of dental sepsis arising spontaneously or after dental surgery. The clinician should be familiar with its presentation and have a high index of suspicion, because late recognition and delay in its treatment can increase the associated morbidity and mortality. Surgical procedures and in particular maxillofacial surgery have also been known to trigger varicella zoster reactivation resulting in Hunt syndrome. Some patients develop the characteristic rash several days after the onset of facial weakness, so that Hunt syndrome may initially be misdiagnosed as Bell's palsy. We highlight the difficulties in diagnosing Hunt syndrome and argue the case for early treatment of all patients with Hunt syndrome and Bell's palsy with a combination of systemic steroids and antiviral drugs.