Long-term nivolumab treatment possibly associated with aseptic meningitis.

Nivolumab is a programmed death-1 receptor blocker within the family of medications called immune checkpoint inhibitors (ICIs). Although generally well tolerated, cases of immune-related adverse events (irAEs) have been reported. We present a case of a man being treated with nivolumab for renal cell carcinoma who presented to the emergency department with problems of headache, fever and disorientation. After extensive evaluation, a diagnosis of immunotherapy-induced aseptic meningitis was considered more probable than infectious. Due to stable clinical status, no treatment was initiated, and the patient's condition improved spontaneously. The patient was discharged home. To date, only a handful of prior cases of nivolumab-induced meningitis have been reported. Our case demonstrates that irAEs can occur years after the initiation of ICIs. This was a milder presentation of a neurological irAE that resolved spontaneously with watchful waiting, showing that irAEs are likely an evolving spectrum of disease for which clinicians should be aware.

Complement Factor I Gene Variant as a Treatable Cause of Recurrent Aseptic Neutrophilic Meningitis: A Case Report.

Mutations in the complement factor I (CFI) gene have previously been identified as causes of recurrent CNS inflammation. We present a case of a 26-year-old man with 18 episodes of recurrent meningitis, who had a variant in CFI(c.859G>A,p.Gly287Arg) not previously associated with neurologic manifestations. He achieved remission with canakinumab, a human monoclonal antibody targeted at interleukin-1 beta.

Clinical Course Associated with Aseptic Meningitis Induced by Intravenous Immunoglobulin for the Treatment of Multisystem Inflammatory Syndrome in Children.

Aseptic meningitis is a rare but potentially serious complication of intravenous immunoglobulin treatment. In this case series, meningitic symptoms following intravenous immunoglobulin initiation in patients with multisystem inflammatory syndrome were rare (7/2,086 [0.3%]). However, they required the need for additional therapy and/or readmission.

Aseptic meningitis after amenamevir treatment for herpes zoster ophthalmicus with oculomotor nerve palsy in a patient taking immunosuppressant.

A 79-year-old woman presented with vomiting after being prescribed amenamevir by her primary care physician. She had a medical history of rheumatoid arthritis and was administered prednisolone and methotrexate. She was finally diagnosed with herpes zoster ophthalmicus and aseptic meningitis, and intravenous antiviral therapy was initiated. However, the patient developed oculomotor nerve palsy on the 11th day of hospitalization. In this case, there was a time lag between the administration of antiviral drugs and clinical improvement. Our case suggests the necessity of selecting antivirals, especially in high-risk cases of CNS complications, to avoid the low intracerebral transferability of antiviral drugs, including amenamevir.

The impact of cerebrospinal fluid viral polymerase chain reaction testing on the management of adults with viral meningitis: A multi-center retrospective study.

The aim of this study was to evaluate the role of viral polymerase chain reaction (PCR) testing in patients with aseptic meningitis and identify opportunities for improvement in clinical management. All cerebrospinal fluid samples collected in 1 year from four teaching hospitals in Sydney, Australia, were reviewed. Patients with aseptic meningitis were selected, and clinical and diagnostic features, hospital length of stay (LOS), and treatment were analyzed. Identifying a cause by viral PCR did not reduce hospital LOS (median 3 days) or antibiotic use (median 2 days), but the turnaround time of the PCR test correlated with LOS (Rs = 0.3822, p = 0.0003). Forty-one percent of patients received intravenous acyclovir treatment, which was more frequent in patients admitted under neurologists than infectious diseases physicians (56% vs. 24%; p = 0.013). The majority of patients did not have investigations for alternative causes of aseptic meningitis such as human immunodeficiency virus and syphilis if the viral PCR panel was negative. The benefit of PCR testing in aseptic meningitis in adults in reducing LOS and antibiotic use is unclear. The reasons for unnecessary aciclovir use in meningitis syndromes require further assessment.

Fabry Disease with Aseptic Meningitis: A Case Series and Literature Review of an Underestimated Clinical Presentation.

OBJECTIVE: Fabry disease (FD) is an X-linked lysosomal storage disease caused by the mutation in the α-galactosidase A gene that leads to a consequently decreased α-galactosidase A enzyme activity and a series of clinical presentations. However, FD accompanied with aseptic meningitis can be relatively scarce and rarely reported, which leads to significant clinical misdiagnosis of this disease. METHODS: Sixteen patients diagnosed with FD based on a decreased activity of α-galactosidase A enzyme and/or genetic screening were identified through a 6-year retrospective chart review of a tertiary hospital. Clinical presentations, brain magnetic resonance imaging, cerebrospinal fluid analysis, treatment and outcome data were analyzed in cases of aseptic meningitis associated with FD. RESULTS: Three out of 16 cases exhibited aseptic meningitis associated with FD. There was one female and two male patients with a mean age of 33.3 years. A family history of renal failure or hypertrophic cardiomyopathy was found in 3 cases. All cases presented with a persistent or intermittent headache and recurrent ischemic stroke. The cerebrospinal fluid analyses showed mild pleocytosis in 2 patients and an elevated level of protein in all patients. Cerebrospinal fluid cytology revealed activated lymphocytes, suggesting the existence of aseptic meningitis. In the literature review, up to 9 cases presenting with FD and aseptic meningitis were found, which bore a resemblance to our patients in demographic and clinical characteristics. CONCLUSION: Our cases suggested that aseptic meningitis in FD might be under-detected and easily misdiagnosed, and should be more thoroughly examined in further cases.

Aseptic Meningitis after Amenamevir Treatment for Herpes Zoster in the First Branch of the Trigeminal Nerve.

Amenamevir has been approved for the treatment of herpes zoster (HZ); however, its therapeutic efficacy against central nervous system (CNS) infection may be insufficient due to its low spinal fluid permeability. We herein report a case of aseptic meningitis in a 91-year-old Japanese man treated with amenamevir for HZ in the trigeminal nerve region. Several cases of CNS infection have been reported in patients receiving amenamevir treatment for HZ. Patients with CNS complications often have skin rashes near the trigeminal region. Thus, we should be alert for signs of CNS infection when administering amenamevir to patients with such rashes.

Aseptic meningitis as initial manifestation of systemic lupus erythematosus: Case series.

Aseptic meningitis is a rare presentation of systemic lupus erythematosus (SLE). High index of suspicion is crucial when there is suboptimal response to the initial standard meningitis treatment and presence of connective tissue disease symptoms. We report 3 cases of aseptic meningitis as the main initial presentation of SLE. The diagnosis of SLE as the underlying cause of the aseptic meningitis was supported by the clinical, laboratory and radiological findings. All patients showed good response after treated with immunosuppressant therapy.

[Restatment. Mollaret's meningitis]. / la Méningite de Mollaret.

MOLLARET MENINGITIS Benign recurrent lymphocytic meningitis, also called Mollaret's Meningitis (MM), is a rare disease most commonly due to HSV-2 virus. Twenty to 30% of patients presenting a first meningitis due to HSV-2 will have recurrent meningitis. This pathology is characterized by recurrent attacks of sud-den onset meningitis with complete recovery, and intervals, free of any symptoms. The majority of patients do not report a history of genital herpes. The diagnosis is based on the clinic and analysis of the cerebrospinal fluid (CSF), which shows aseptic lymphocytic meningitis. A positive PCR for HSV-2 allows a diagnosis with certainty. Facing a negativ PCR, the diagnosis of MM is established after excluding other causes of recurrent lymphocytic meningitis. The pathophysiology is not well known but is linked to the reactivation of the HSV-2 virus located in the sacral ganglia of sensory neurons in a latent state after the primary genital infection. Treatment of a first episode of MM with HSV-2 is based on antivirals. But no treatment has been shown to be effective in reducing the duration of recurrences or the frequency of recurrences. The prognosis is excellent with a tendency to a spontaneous decrease of the frequency of recurrences over time. It is important to know this pathology, in order to avoid diagnostic wandering and the multiplication of invasive examinations.

LA MÉNINGITE DE MOLLARET La méningite récurrente lymphocytaire bénigne, ou méningite de Mollaret (MM), est une maladie rare le plus souvent attribuée au virus HSV2. Elle concerne 20 à 30 % des patients ayant fait une première méningite à HSV2. Cette pathologie se caractérise par la récurrence de syndromes méningés francs et d'apparition brutale, d'évolution spontanément favorable, espacés d'intervalles libres de tout symptôme. La majorité des patients ne rapporte pas d'antécédent d'herpès génital. Le diagnostic repose sur la clinique et l'analyse du LCR, qui montre une méningite lymphocytaire aseptique. Une PCR positive pour HSV2 pose le diagnostic de certitude. Face à une PCR négative, le diagnostic de MM est établi après exclusion des autres causes de méningite récurrente lymphocytaire. La physiopathologie est peu connue mais serait liée à la réaction du virus HSV2, localisé dans les ganglions sacrés des neurones sensitifs à l'état latent après la primo-infection génitale. Le traitement d'un premier épisode de MM à HSV2 repose sur les antiviraux, mais aucun traitement n'a démontré son efficacité pour réduire la durée ou la fréquence des récurrences. Le pronostic est excellent, avec une tendance à la diminution spontanée de la fréquence des récurrences au cours du temps. Il est important de connaître cette pathologie afin d'éviter une errance diagnostique et la multiplication d'examens invasifs.

Meningitis retention syndrome caused by varicella zoster virus in a patient without a rash: a case report.

BACKGROUND: Meningitis retention syndrome (MRS) is a rare condition that presents with acute urinary retention as a complication of aseptic meningitis. Cases of MRS due to varicella zoster virus (VZV) infection without a rash are rare. We report the case of a patient who had no signs of meningitis or VZV infection, including a rash. CASE PRESENTATION: A 58-year-old man presented with dysesthesia of the lower limbs and acute urinary retention. He had fever but no rash and no signs of meningitis. He was diagnosed to have VZV infection based on the detection of VZV DNA in the cerebrospinal fluid. He responded satisfactorily to a course of intravenous acyclovir and experienced no sequelae during a 2-year follow-up period. CONCLUSION: MRS due to aseptic meningitis of viral origin should be considered in the differential diagnosis of acute urinary retention even in the absence of specific signs and symptoms of meningitis or a suggestive rash.

Aseptic meningitis and hydrocephalus secondary to neurosarcoidosis.

A 53-year-old woman presented to hospital with gait instability, urinary incontinence and confusion. She had a 4-month history of headache, blurred vision, personality change and memory problems. Magnetic Resonance Imaging of the brain after contrast application showed tectal plate and occipital enhancement, as well as a known hydrocephalus. Cerebrospinal fluid showed aseptic meningitis with no evidence of clonal expansion. After further imaging that showed generalised lymphadenopathy and subsequent tissue biopsy that showed granulomatous lymphadenitis, she was diagnosed with neurosarcoidosis. She was treated with steroids which resulted in immediate cognitive and motor improvements as well as resolution of her urinary incontinence. We discuss the features of this case that pointed towards neoplastic, infective and other autoimmune aetiologies. We describe how they were excluded and provide the rationale for our treatment. This case demonstrates an important sequela sarcoidosis, and we conclude by recommending a multidisciplinary approach towards its diagnosis and management.

Aseptic Meningitis-retention Syndrome Associated with Tocilizumab in a Patient with Idiopathic Multicentric Castleman Disease.

This is the first report of tocilizumab-associated meningitis-retention syndrome in a patient with idiopathic multicentric Castleman disease. A 57-year-old man presented with headache, nuchal rigidity, impaired consciousness, pyramidal tract signs and urinary retention. A cerebrospinal fluid examination revealed increased cell counts and protein levels. These symptoms were improved by intravenous methylprednisolone. Tocilizumab-associated meningoencephalitis has been reported in patients with rheumatoid arthritis and juvenile idiopathic arthritis but not with multicentric Castleman disease. This case presents evidence of the increased probability of meningitis as a neurological complication of tocilizumab administration.

Aseptic meningitis as the initial presentation of Leptospira borgpetersenii serovar Tarassovi: two case reports and a literature review.

BACKGROUND: Leptospirosis is a zoonotic illness caused by pathogenic spirochetes of the genus Leptospira. The disease spectrum ranges from a mild influenza-like presentation to a more serious Weil's syndrome. Leptospirosis rarely presents as a primary neurological syndrome. We report two cases of Leptospira borgpetersenii serovar Tarasssovi presenting as aseptic meningitis in Sri Lanka. CASE PRESENTATION: We describe case reports of two patients presenting as symptomatic aseptic meningitis due to neuroleptospirosis. Both patients had significant neurological involvement at presentation in the absence of common clinical features of leptospirosis. These patients were initially managed as bacterial or viral meningitis and leptospirosis was suspected due to a history of exposure to contaminated water. Subsequently, they were diagnosed to have neuroleptospirosis by positive Leptospira serology and both patients gained full recovery. CONCLUSION: Our report highlights the importance of considering leptospirosis as a differential diagnosis in patients with aseptic meningitis in endemic settings. Obtaining a detailed occupational and recreational history is helpful in diagnosing neuroleptospirosis promptly. We report the association of Leptospira borgpetersenii serovar (sv.) Tarassovi (strain bakeri) in causing aseptic meningitis, which has not been reported to the best of our knowledge.

Benign Recurrent Aseptic Meningitis (Mollaret's Meningitis) in an Elderly Male: A Case Report.

Mollaret's meningitis is an aseptic recurrent benign lymphocytic meningitis lasting 2-5 days and occurs over years with spontaneous complete resolution of symptoms between episodes. An 88 years-old-male presented with acute onset headache, lethargy and altered sensorium after a recent ear infection. He had multiple similar episodes in the past, each preceded by ear or sinus infection with cerebrospinal fluid finding consistent with aseptic meningitis. However, no specific causative agent was ever identified. He was confused, disoriented and lethargic with normal vitals and systemic examination. Blood tests showed leukocytosis with neutrophilia. Cerebrospinal fluid analysis revealed increased cell count with lymphocyte predominance, elevated protein and negative polymerase chain reaction. Magnetic resonance imaging of brain showed chronic small vessel ischemic changes. He fulfilled the Bruyn's criteria for clinical diagnosis. He was empirically administered acyclovir during hospitalization and was discharged without prophylactic antiviral due to negative cerebrospinal fluid analysis, culture, and multiplex polymerase chain reaction.

Meningitis aséptica secundaria a la administración de inmunoglobulina / Aseptic meningitis following immunoglobulin therapy

Introducción: la meningitis aséptica es una entidad infrecuente y multifactorial, siendo raros los efectos secundarios a la administración de inmunoglobulina. Objetivo: reportar el caso de una paciente hospitalizada en el servicio de pediatría en un hospital de Bogotá. Discusión: las principales causas de la entidad son virales. Aunque el uso de inmunoglobulina en pediatría es seguro, uno de sus efectos adversos menos comunes es la meningitis aséptica. Están descritas las posibles teorías fisiopatológicas que podrían explicar su desenlace. Conclusión: la meningitis aséptica puede corresponder a un efecto secundario al uso de inmunoglobulina en pediatría.

Introduction: aseptic meningitis is a rare and multifactorial entity and side effects of immunoglobulin therapy are rare. Objective: to report the case of a female patient hospitalized in the pediatrics service in a hospital in Bogotá. Discussion: the most common cause of aseptic meningitis is viral infection. Although the use of immunoglobulin therapy in pediatric patients is safe, one of its less common adverse effects is aseptic meningitis. The pathophysiological theories that could explain its outcome have been described. Conclusion: aseptic meningitis may be a side effect to the use of immunoglobulin in pediatric practice.

Drug-induced meningitis: A review of the literature and comparison with an historical cohort of viral meningitis cases.

BACKGROUND: Drug-induced aseptic meningitis (DIAM) is potentially insufficiently considered by clinician, being of rare etiology, with there being no previously published exhaustive study describing its clinical and biological features. METHODS: Two independent academic clinicians searched all the case reports of DIAM from 1995 until 15th April, 2017. The search was limited to studies performed in humans, published in English or French. Clinical and biological data of subjects were compared with those of patients with documented viral meningitis. RESULTS: One hundred and fifty-one case reports fulfilled our inclusion criteria. Non-steroidal anti-inflammatory drugs were the commonest drug cause of AM n=49, followed by antibiotics n=46, biotherapy n=19 and finally immunomodulators n=15. The clinical and biological presentation of DIAM varies according to the causative etiological drug, especially with respect to the interval between exposure and presentation and cerebrospinal fluid (CSF) pleiocytosis. Clinical symptoms associated with meningitis were more prevalent in viral meningitis than in DIAM, except for fever and signs of encephalitis. Cerebrospinal fluid examination in DIAM reveals an increased CSF white cell count and an increased proportion of neutrophils and protein, compared with viral meningitis. DISCUSSION: We present an extensive review of the DIAM case reports, and highlight their clinical and biological characteristics according to the drugs involved. While comparing for the first time their characteristics with those of viral meningitis, this review hopes in facilitate earlier diagnosis and management of DIAM in clinical practice.