Chronic Enterovirus Meningoencephalitis in Prolonged B-Cell Depletion After Rituximab Therapy: Case Report.

OBJECTIVES: Persistent impaired immunity is possible even years after B-cell depleting therapies. This may favor the occurrence of infections, including infectious meningitis and encephalitis. In this study, we report a case of chronic enterovirus meningoencephalitis in prolonged B-cell depletion years after rituximab therapy. METHODS: This is a case report from a German academic hospital. In addition to repeated clinical examinations, repeated brain MRI and extended CSF and laboratory diagnostics were performed. We used the CARE checklist when writing our report. RESULTS: A 38-year-old man presented with high fever (>40°C), severe headache, and progressive neurologic and cognitive deficits. As result of previous lymphoma therapy with rituximab years ago, prolonged B-cell aplasia was detected. To restore humoral immunity, the patient received repeated infusions of immunoglobulins. In the end, a complete restitution of the physical and mental condition was achieved with the established therapy. DISCUSSION: This case report should emphasize the importance of assessing humoral immunity even years after B-cell depletion therapy, especially in case of opportunistic infections.

Cerebrospinal Fluid Interleukin-6 in Immune Checkpoint Inhibitor-Induced Autoimmune Meningoencephalitis.

Immune checkpoint inhibitors (ICIs) have proven clinical benefits in various advanced cancers. However, despite their significant therapeutic efficacy, ICIs induce immune-related adverse events. Among these events, autoimmune meningoencephalitis often has severe effects on patients' outcomes, but its specific clinical features are still unclear. Here, we report two cases of ICI-associated meningoencephalitis with elevated interleukin-6 (IL-6) levels in the cerebrospinal fluid (CSF). A 47-year-old woman (Case 1) with renal cell carcinoma developed severe headache after a seventh nivolumab administration. A neurological examination revealed jolt accentuation signs and hyperreflexia in all extremities. CSF analysis revealed a high IL-6 value (6,620 pg/mL) with marked pleocytosis. A 70-year-old woman (Case 2) who received an initial administration of nivolumab plus ipilimumab for renal cell carcinoma developed alterations of consciousness. She presented with impaired consciousness, neck stiffness, and hyperreflexia in all extremities. CSF analysis demonstrated a high IL-6 value (49.3 pg/mL) with mild pleocytosis. Both patients were treated with steroid pulse therapy (methylprednisolone 1,000 mg/day, 3 days), followed by the administration of oral predonisolone. The symptoms and laboratory findings improved in both cases. CSF IL-6 values were proportional to the severity of meningoencephalitis and other clinical parameters. These findings may help elucidate the mechanisms of central nervous system complications that are caused by ICIs.

Recognising immunotherapy-induced meningoencephalitis: a case during treatment for primary metastatic melanoma of the bladder neck.

Although novel immunotherapy has shown promise for patients with melanoma, a more activated state of the immune system may lead to adverse systemic effects. Immunotherapy-induced meningoencephalitis is a rare and seldom reported adverse effect of immunotherapy but with the expanding role of immunotherapy in cancer treatments it must be recognised. Patients receiving immunotherapy should receive a proper warning about the potential for this life-threatening condition. Herein, we report a patient in his 70s with neurological changes after his second treatment with dual immunotherapy for a primary metastatic melanoma of the bladder neck.

Micafungin injection for the treatment of invasive candidiasis in pediatric patients under 4 months of age.

INTRODUCTION: Neonates and young infants with invasive candidiasis are particularly at increased risk of dissemination including hematogenous Candida meningoencephalitis. The echinocandins including micafungin have emerged as a preferred agent in most cases of candidemia and invasive candidiasis but data in pediatric patients under 4 months of age are limited. AREAS COVERED: In this report, we review the micafungin use in infants younger than 4 months of age. Animal studies as well as clinical data that support its use in neonatal candidiasis are reviewed. In addition, the status of FDA approval and the rationale of micafungin dosing recommendations in infants <4 months are discussed. EXPERT OPINION: A dose of 4 mg/kg was approved for treatment of candidemia, Candida peritonitis and abscesses excluding meningoencephalitis or ocular involvement in patients younger than 4 months of age. However, because of the risk of central nervous system dissemination as well as the difficulty in establishing this diagnosis, this dose is inadequate to treat ill infants with candidemia. More studies are needed to establish the safety and efficacy of micafungin daily dose of at least 10 mg/kg in infants younger than 4 months of age when hematogenous Candida meningoencephalitis or ocular involvement cannot be excluded.

[A case of meningoencephalitis that developed during nivolumab use].

A 72-year-old woman developed a fever and consciousness disturbance after completing 8 courses of nivolumab for lung adenocarcinoma. A cerebrospinal fluid test showed an increased cell count, but bacterial culture, herpes simplex virus-polymerase chain reaction, acid-fast staining, and cytology were negative; serum paraneoplastic syndrome-related antibody was also negative. Serum and cerebrospinal fluid specimens were positive for anti-glutamate receptor (GluR) antibody, and fluid-attenuated inversion recovery images on head magnetic resonance imaging showed a high signal intensity at the right parietal lobe. The condition was determined to be immune-mediated encephalitis, and pulse steroid therapy was performed. The symptoms promptly improved after treatment. The patient in the present case was anti-GluR antibody-positive but was determined to have nivolumab-related encephalitis based on the clinical course. The use of immune checkpoint inhibitors has become widespread in recent years, although it can occasionally lead to encephalitis. We herein report our experience with immune checkpoint inhibitor-related encephalitis, which is seldom reported in Japan.

Herpes Simplex Virus Meningoencephalitis Following Pulse-Dose Methylprednisolone: A Case Report and Literature Review.

BACKGROUND Several cases of herpes simplex virus type 1 meningoencephalitis (HSVE) have been reported in patients receiving steroids, but the exact contribution of steroids to the disorder remains unclear because other risk factors, such as chemotherapy, brain radiation, or surgery, were present in almost all cases. CASE REPORT We report the case of a 76-year-old man who developed HSVE following the administration of pulse-dose steroids. The patient had occupational asbestos exposure and a chronic interstitial lung disease of unclear etiology (sarcoidosis versus hypersensitivity pneumonitis) and was admitted for acute-on-chronic respiratory failure requiring mechanical ventilation. After a negative infectious workup and several days of antibiotics without improvement, pulse-dose steroids were administered. In the following days, the patient developed a fever and worsening encephalopathy. A lumbar puncture showed elevated nucleated cells and positive polymerase chain reaction for herpes simplex virus 1 in the cerebrospinal fluid, confirming the diagnosis of HSVE. Acyclovir treatment was initiated, but the patient later died as a result of persistent severe encephalopathy and respiratory failure with an inability to wean mechanical ventilation. CONCLUSIONS Clinicians should keep in mind that HSVE is a potential complication of steroids and carefully consider the benefit/risk ratio of pulse-dose steroids, taking into account associated factors of immunosuppression. A high level of awareness should be especially maintained in critically ill patients because of associated risk factors (critical illness immune paralysis) and because neurological signs of HSVE may be missed in mechanically ventilated, sedated patients.

[A case of meningoencephalitis and polyradiculoneuropathy induced by combination therapy with ipilimumab and nivolumab].

A 76-year-old man with renal cell carcinoma exhibited consciousness disturbance and high fever after two cycles of combination therapy with ipilimumab and nivolumab. His cerebrospinal fluid (CSF) showed a protein concentration of 385 mg/dl, a cell count of 147/mm3, an interleukin-6 concentration of 1,280 pg/ml, and an adenosine deaminase concentration of 24.8 U/l. Contrast-enhanced FLAIR images were notable for diffuse meningeal enhancement. He was diagnosed with meningoencephalitis caused by an immune-related adverse event from immune checkpoint inhibitors (ICIs). His symptoms improved after repeated intravenous methylprednisolone pulse therapy and oral prednisolone. The meningeal enhancement disappeared, and the CSF findings became almost normal. As consciousness levels improved, we observed quadriplegia and peripheral neuropathy with antiganglioside antibodies, which led to a diagnosis of polyradiculoneuropathy. This is a rare case of a patient with overlapping meningoencephalitis and polyradiculo-neuropathy induced by ICIs.

Fingolimod-related cryptococcal meningoencephalitis and immune reconstitution inflammatory syndrome in a patient with multiple sclerosis.

Fingolimod is an oral medication for multiple sclerosis that sequesters certain subsets of lymphocytes in lymph nodes, reducing egress into blood and their subsequent CNS migration. The initial multi-site randomized Phase III controlled trials found rates of infection similar to those in control groups. However, post-marketing surveillance has revealed an association with several opportunistic infections, including cryptococcosis. We report a case of fingolimod-related cryptococcal meningoencephalitis and IRIS after drug discontinuation and suggest a surveillance and risk mitigation strategy.

Glial fibrillary acidic protein (GFAP) associated autoimmune meningoencephalitis in a patient receiving nivolumab.

Immune checkpoint inhibitors (ICIs) represent a major development in cancer treatment, allowing for improved survival and disease control in an expanding number of cancer types. Due to their mechanism of disrupting immunologic homeostasis, ICIs are frequently associated with adverse effects, termed immune related adverse effects (irAE). These side effects can affect any organ system, including the central and peripheral nervous systems. We present a case of a 47 year old man with stage IIIc metastatic melanoma who received 3 cycles of nivolumab (a monoclonal antibody inhibitor of programmed cell death protein 1 (PD-1)). After completing the third cycle, he presented with a meningoencephalitis clinical picture with an inflammatory cerebrospinal fluid (CSF) and normal MRI. He was found to have a positive anti-glial fibrillary acidic protein (GFAP) autoantibody in his CSF by immunofluorescent assay (IFA) and cell based assay (CBA) which confirmed a diagnosis of anti-GFAP autoimmune encephalitis. He was treated with immunotherapy and made a full recovery. In this report, we present the first reported case of anti-GFAP autoimmune encephalitis associated with ICI therapy and provide a brief review of the literature.

[A case of meningoencephalitis associated with pembrolizumab treated for squamous cell lung cancer].

A 61-year-old man with squamous cell lung cancer was admitted to our hospital because of consciousness disturbance after treated with pembrolizumab. Cerebrospinal fluid examination revealed increased protein level (209.2 mg/dl) and lymphocytic pleocytosis(79/µl). He was diagnosed as a meningoencephalitis probably caused by an immune-related adverse event (irAE) of immune checkpoint inhibitors (ICIs), and was successfully treated with 1,000 mg methylprednisolone intravenously for 3 days twice and the consequent oral 1 mg/kg prednisolone. As ICIs, which activate the immune systems, are becoming important choices of the treatments against malignancies, we should keep the possibility of irAE in mind and, when needed, start the treatment as soon as possible.

Meningoencefalitis recurrente por alopurinol / Recurrent meningoencephalitis due to allopurinol

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Cytomegalovirus meningoencephalitis after rituximab treatment for primary central nervous system lymphoma.

The efficacy and safety of rituximab against B-cell lymphomas is well established. However, there has been an increased incidence of infectious complications after rituximab treatment, mostly hepatitis B reactivation and progressive multifocal leukoencephalopathy. This is the case of a 67-year-old patient with primary central nervous system lymphoma, who developed cytomegalovirus meningoencephalitis after receiving high-dose chemotherapy and rituximab. As there was no evidence of lymphoma relapse or additional immunosuppression, besides his previous treatment, an association between rituximab and cytomegalovirus meningoencephalitis cannot be ruled out.