Herpesviral encephalitis associated with bortezomib use in a patient with multiple myeloma and associated light-chain amyloidosis.

INTRODUCTION: Bortezomib is proteasome inhibitor used in multiple myeloma treatment. The reactivation of herpes simplex virus (HSV) and varicella-zoster virus (VZV) during bortezomib-based therapy is a well-known adverse event. Antiviral prophylaxis is mandatory. Nevertheless, reports of herpesviral encephalitis are scarce. CASE REPORT: A 57-year-old multiple myeloma patient who during CyBorD protocol (Bortezomib, cyclophosphamide, and dexamethasone), after a transient suspension of antiviral prophylaxis presented progressive headaches unresponsive to conventional analgesics, asthenia, fever, episodic visual hallucinations, and vesicular lesions in the right supraorbital and frontal region. Herpetic encephalitis was diagnosed after detecting herpes zoster in cerebrospinal fluid. MANAGEMENT & OUTCOME: The patient was treated with acyclovir 500mg every 6 hours for 21 days, and subsequent valacyclovir prophylaxis achieving an excellent clinical evolution. Anti-myeloma treatment was changed to lenalidomide and dexamethasone achieving a durable complete response. Herpesviral encephalitis is a rare but severe complication associated with the use of Bortezomib, especially when patients did not receive acyclovir prophylaxis. However, a rapid detection based on the clinical suspicion, and the prompt start of treatment, may lead to overcome this adverse event.

Virus reactivation after immunotherapy of anti-NMDAR encephalitis secondary to herpes simplex encephalitis: A case report.

Herpes simplex encephalitis is the most common cause of sporadic fatal encephalitis. More than half of patients with herpes simplex encephalitis will die and the vast majority of survivors have severe neurologic sequelae without effective antiviral therapy. Some people experience relapses such as secondary anti-N-methyl-d-aspartate receptor encephalitis despite appropriate antiviral treatment. It is rare that virus reactivation after immunotherapy of anti-N-methyl-d-aspartate receptor encephalitis after herpes simplex encephalitis. In the present study, we retrospectively review one patient who showed this rare situation.

Herpes simplex virus encephalitis in a patient receiving ustekinumab associated with extensive cerebral oedema and brainshift successfully treated by immunosuppression with dexamethasone.

Herpes simplex virus (HSV) encephalitis affects 2-4 people per million/year. Immunocompomised patients can have atypical presentations of HSV encephalitis, including a lack of cerebrospinal fluid (CSF) pleocytosis. We present the case of a patient who was receiving ustekinumab therapy for psoriasis which inhibits interleukin (IL)-12 and IL-23 signalling pathways. The initial presentation was suggestive of encephalitis, but he was discharged prior to the reporting of HSV positivity due to the lack of CSF pleocytosis. On representation, he had worsening symptoms and imaging showed midline shift, indicating cerebral oedema despite the immunosupressant effects of ustekinumab. He required intensive care unit support and treatment with high dose aciclovir and dexamethasone; after a month of treatment he made a good recovery. This case is the first to report a link between ustekinumab and HSV encephalitis, and also emphasises that imunocompromised patients can lack CSF pleocytosis and develop significant cerebral oedema which responds to immune suppression.

Potential risk of developing herpes simplex encephalitis in patients treated with sildenafil following primary exposure to genital herpes.

Herpes simplex encephalitis (HSE) is associated with significant mortality and morbidity. As a consequence of HSE, up to 75% of infected individuals die or experience irreversible neurological damage. While the pathogenesis of the disease is unknown, it is traditionally hypothesized that the viral infection occurs by neuronal transmission directly from peripheral sites. Non-neuronal modes of infection have generally been overlooked as the brain is protected by the blood-brain-barrier (BBB). The BBB poses an effective barrier to pathogens as well as to drugs such as chemotherapies. In the pursuit to deliver chemotherapeutic agents to the brain, several studies demonstrated that phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, may increase the permeability of the BBB enabling successful delivery of chemotherapeutic agents to the brain. In this communication, we report a case of HSE infection in a 62-year-old man, which we suspect was facilitated by the use of sildenafil during a primary genital herpes simple virus (HSV) infection. Due to large number of patients treated with PDE5 inhibitors for erectile dysfunction and the high incidence of genital HSV infection in the general population, a larger study should examine the potential risk of developing HSE in patients treated with PDE5 inhibitors.

Herpes simplex virus-1 encephalitis induced by chemoradiotherapy and steroids in an esophageal cancer patient: a case report.

BACKGROUND: Systemic chemotherapy combined with steroids used as prophylactic antiemetics have been reported to induce immunosuppression. Further, herpes simplex virus-1 (HSV-1) infection has been reported to occur in patients with small cell carcinomas after chemoradiotherapy that includes brain irradiation. Here, we report a case of HSV-1 encephalitis that occurred in a patient undergoing chemoradiotherapy for advanced esophageal cancer. CASE PRESENTATION: A 77-year-old woman received chemoradiotherapy (5-fluorouracil, 700 mg/m(2); cisplatin, 70 mg/m(2); and radiotherapy, 60 Gy in total) for stage III esophageal cancer. The total radiation dose was administered concurrently with the first two courses of chemotherapy, together with dexamethasone as a prophylactic antiemetic. Two days before completion of the fourth course of chemotherapy, the patient developed acute neurological symptoms of disorientation, clouding of consciousness, and fever. T2-weighted magnetic resonance imaging showed a high intensity area in the bilateral temporal lobes and insular cortex. Furthermore, DNA PCR testing of cerebrospinal fluid showed clear positivity for HSV-1 DNA, and the patient was diagnosed with herpetic encephalitis. Intravenous administration of acyclovir for 3 weeks led to gradual improvement of consciousness, and the patient was able to respond to verbal cues. CONCLUSION: In advanced esophageal cancer patients, standard treatment involves chemoradiotherapy and surgery. However, primary infection with or reactivation of endogenous latent HSV-1 in the brain cortex during chemoradiotherapy combined with administration of a steroid may compromise the benefits of treatment.

Central nervous system herpes simplex and varicella zoster virus infections in natalizumab-treated patients.

We report on 20 natalizumab-treated patients with multiple sclerosis who developed laboratory-confirmed central nervous system (CNS) herpesvirus infections. In addition to progressive multifocal leukoencephalopathy, other CNS opportunistic infections have been rarely reported during natalizumab treatment. We encourage heightened awareness due to the risk for serious outcomes.

Herpes encephalitis during natalizumab treatment in multiple sclerosis.

In this case report we describe the first non-fatal herpes simplex virus encephalitis (HSE) case with natalizumab for multiple sclerosis (MS). A 36-year-old woman, previously treated with immunomodulatory and immunosuppressive drugs for MS, developed acute encephalitis after 6 monthly natalizumab perfusions. Brain imaging demonstrated suggestive bi-temporal lesions. Herpes simplex virus type-1 DNA was detected in cerebrospinal fluid. The patient improved gradually after a 21-day course of intravenous acyclovir, but neuropsychiatric changes remained 5 months later. Our non-fatal case of HSE and other reported cases of herpes infections provide evidence of an increased risk with natalizumab and point to the need for clinicians to maintain awareness.

Herpes simplex encephalitis presenting after steroid treatment of panuveitis.

A 62-year-old woman with an autoimmune disease presented with panuveitis and was treated with immune suppression. She subsequently developed herpetic acute retinal necrosis and later died of herpes simplex encephalitis. Acute retinal necrosis usually occurs months to years after herpes simplex encephalitis. In our case, the ocular findings were present for 5 weeks before the encephalitis presented. To our knowledge, this is the first Australian case of acute retinal necrosis preceding herpes simplex encephalitis.