Cerebrospinal Fluid Eosinophilia Research Articles

Cerebrospinal fluid eosinophils in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease

BackgroundEosinophils in cerebrospinal fluid (CSF) are an uncommon finding most often associated with parasitic infections, but have also been described in some neuroinflammatory disorders. Eosinophilic infiltration is not thought to be a typical feature of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We aim to describe the rate of CSF eosinophil positivity in a cohort of pediatric MOGAD patients. MethodsSingle-center retrospective chart review of pediatric MOGAD patients. Clinical and laboratory data was collected from the electronic medical record and analyzed. ResultsOf 46 pediatric patients with positive serum myelin oligodendrocyte glycoprotein antibody (MOG-IgG) identified, 38 patients fulfilling internationally proposed MOGAD diagnostic criteria were included for analysis. 6 patients with MOGAD were excluded as no CSF data was available, and 2 patients with positive MOG-IgG but diagnosis more consistent with MS were excluded. Median age was 7.3 years, and 19/38 (50 %) were female. Acute disseminated encephalomyelitis (ADEM) was the most common presenting phenotype (23/38, 61 %), and other phenotypes included optic neuritis (10/38, 26 %), transverse myelitis (3/38, 8 %), and neuromyelitis optica spectrum disorder (NMOSD) (2/38, 5 %). 12 of 36 (33 %) patients with all lumbar puncture (LP) data available had CSF eosinophils present, with eosinophil mean of 3 % and range from 1 % to 18 % of CSF while blood cells. ConclusionCSF eosinophils were present in one third of pediatric MOGAD patients, which is a higher rate than previously reported in either MOGAD or aquaporin-4 antibody positive NMOSD cohorts. Understanding the CSF composition of pediatric MOGAD patients helps to facilitate more prompt diagnosis and treatment and may shed light onto underlying pathologic mechanisms of disease with the goal to inform future therapeutic targets.

Case of autoimmune GFAP astrocytopathy with eosinophils in the cerebrospinal fluid

Cerebrospinal fluid (CSF) eosinophilia is associated with a narrow differential, primarily including parasitic and fungal infections, neoplasm, and chemical meningitis. It has rarely been reported in neuroinflammatory conditions including as a finding of CSF cytology in two autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy cases. Here we describe a case of autoimmune GFAP astrocytopathy with classic clinical and radiographic features as well as presence of eosinophils in the CSF. This case highlights a potential association of eosinophils in the CSF with autoimmune GFAP astrocytopathy, which may suggest its inclusion in the differential diagnosis of eosinophilic meningitis, encephalitis, or myelitis.

Clinical Characteristics and Treatment Outcome of Eosinophilic Meningoencephalitis in South Indian Children: Experience From a Prospective Registry

BackgroundTo describe the clinical features and therapeutic outcomes of a prospective cohort of children with eosinophilic meningoencephalitis. MethodsChildren admitted with clinical features suggestive of meningitis along with cerebrospinal fluid (CSF) eosinophilia during the period of 14 years (2008 to 2021) were included. Their baseline characteristics, epidemiologic associations, and treatment outcomes were analyzed and compared with the previous studies. ResultsWe identified 25 children (13 males) satisfying the inclusion criteria. The median age at presentation was 3.9 years (range 0.8 to 17 years); 68% were aged less than two years. Fourteen (56%) children had a history of exposure to snails. Most of them presented with fever, headache, irritability, lateral rectus palsy, and early papilledema. Symptoms started three to 42 days (median duration: 14 days) before admission to our center. All children had peripheral eosinophilia, which ranged from 9% to 41%. The mean CSF white blood cell count was 416/mm3 (range 50 to 1245 cells/mm3) with CSF eosinophilia ranging from 11% to 80%. Brain magnetic resonance imaging was done in 24 children and was normal in 15 (62.5%). Leptomeningeal enhancement was seen in two (8.3%) children, and other nonspecific changes were noted in seven (29.1%) children. All children recovered without any neurological deficits with a standard treatment regimen of albendazole and oral steroids. All were asymptomatic at the last follow-up. None of them had any recurrence during the follow-up period. ConclusionWe report one of the largest clinical series of children with eosinophilic meningoencephalitis from an endemic area of South India.

Atypical Presentations of Extraparenchymal Neurocysticercosis.

Neurocysticercosis (NCC) is the most common parasitic infection of the central nervous system and is typically diagnosed through visualization of the cysts in the cerebral parenchyma by neuro-imaging. However, neuro-imaging may not detect extraparenchymal neurocysticercosis (EPNCC), which is a rare manifestation of the disease involving the subarachnoid, meningeal, and intraventricular spaces. We report 2 cases of extraparenchymal neurocysticercosis, and discuss the diagnostic challenges and management of this entity. Two cases were identified through clinical records. Both patients had an insidious onset with slow progression of disease, and presented with papilledema and cerebrospinal fluid (CSF) eosinophilia. One case was diagnosed with spinal cord biopsy. The other was diagnosed with CSF serology and next-generation sequencing-based pathogen analysis. Both patients were treated with ventriculoperitoneal shunt, systemic antiparasitic agents, and immunosuppression. EPNCC is less common than parenchymal NCC. A high level of clinical suspicion is required given its rarity, long incubation period, and slow progression. Diagnosis and treatment can be challenging and requires a multidisciplinary approach.

Peroxisome-Proliferator Activator Receptor γ in Mouse Model with Meningoencephalitis Caused by Angiostrongylus cantonensis.

Peroxisome-proliferator activator receptor γ (PPARγ) has an anti-inflammatory role that inhibits the nuclear factor-κB (NF-κB) pathway and regulates the expressions of pro-inflammatory proteins, whereas its role in parasitic meningoencephalitis remains unknown. In this study we investigated the role of PPARγ and related mechanisms in eosinophilic meningoencephalitis caused by the rat lungworm Angiostrongylus cantonensis. We observed increased protein NF-κB expression in mouse brain tissue using GW9662, which is the specific antagonist of PPARγ, in a mouse model of angiostrongyliasis. Then we investigated NF-κB-related downstream proteins, such as COX-2, NOSs, and IL-1β, with Western blot or enzyme-linked immunosorbent assay and found that the protein expression was upregulated. The results of gelatin zymography also showed that the MMP-9 activities were upregulated. Treatment with GW9662 increased the permeability of the blood-brain barrier and the number of eosinophils in cerebrospinal fluid. These results suggested that in angiostrongyliasis, PPARγ may play an anti-inflammation role in many inflammatory mediators, including NOS-related oxidative stress, cytokines, and matrix metalloproteinase cascade by decreasing the NF-κB action.

Toxocariasis of the Nervous System.

Toxocariasis is a helminthozoonosis caused by the infection of a human host by the larva of Toxocara spp., predominately involving Toxocara canis and Toxocara cati, which are common nematodes in dogs and cats, respectively. Human transmission occurs through contact with animals or by consumption of food contaminated with parasite's eggs. The purpose of this article is to review the current knowledge regarding human neurotoxocariasis. We conducted a systematic review of the existing literature concerning toxocariasis of the nervous system. Clinical spectrum of humantoxocariasisvaries widely from a subclinical course to significant organ morbidity. Clinical course depends on parasitic load, the migration route of the larvae and host response. Human neurotoxocariasis is a relatively rare entity yet associated with severe sequelae. Manifestations include meningitis (usually eosinophilic), encephalitis, myelitis, cerebellar vasculitis, space-occupying lesion, behavioral abnormalities, and optic neuritis. Even though valid diagnostic criteria are lacking, neurotoxocariasis should be suspected in patients with neurologic symptoms and cerebrospinal fluid (CSF) pleocytosis with eosinophilia, positive serology for anti-Toxocara antibodies, in serum and/or CSF, sterile CSF and clinical improvement after antihelminthic treatment. Neurotoxocariasis is treated by benzimidazole components, most frequently albendazole, corticosteroids, or diethylcarbamazine. Parasite larvae migrate through tissues and are able to reach the nervous system causing neurotoxocariasis. Its clinical spectrum varies and includes myelitis, meningoencephalitis, brain abscess, and vasculitis. Neurotoxocariasis should always be suspected in patients with neurologic symptoms accompanied by eosinophilia in blood and/or CSF. Early diagnosis and treatment could prevent long-term neurologic impairment.

Diagnostic importance of eosinophilic meningitis in HIV-positive and HIV-negative patients.

The presence of eosinophils in the cerebrospinal fluid (CSF) should always be considered abnormal. This study aimed to evaluate the causes of eosinophils in the CSF of patients who are HIV positive and HIV negative. This is the first study of eosinophils in the CSF of patients who are HIV-positive. This was a retrospective study of CSF reports from 1996 to 2005, patients were selected based on the presence of eosinophils in the CSF. We analyzed 20,008 CSF reports; eosinophils were present in 5%. The median and interquartile range (IQR) of eosinophils was 2% (1%, 4%). Eosinophilic meningitis (CSF eosinophils≥ 10%) was present in 12% of the samples. The main etiologies were infectious diseases as follows: neurocysticercosis, Cryptococcus sp. meningitis, and acute bacterial meningitis. In HIV-positive cases, all causes were by infectious disease, the main pathogen being Cryptococcus sp. The probability of neurocysticercosis in a patient from an endemic region who is HIV-negative and has CSF eosinophils more than 10% was five times higher compared to a person without eosinophilic meningitis. There was a weak positive correlation between CSF eosinophils and increased serum eosinophils. Among the HIV-negative cases, the most frequent non-infectious causes were cerebrovascular syndromes, of these hemorrhage (91.5%). In the HIV-positive group, there were no cases of non-infectious cerebral disease. CSF eosinophils are suggestive of disease. The causes must be investigated, considering the most prevalent infectious diseases in the region.

Cystoperitoneal Shunt Malfunction in Setting of Rifampin Allergy Presenting as Cerebrospinal Fluid Eosinophilia

Background: Cerebral spinal fluid eosinophilia (CSFe) is correlated with increased risk of cranial shunt malfunctions. Although antibiotics coated shunt catheters have significantly reduced the incidence of infections and associated shunt malfunction, on rare occasion they may contribute to a shunt allergy and become the source of subsequent malfunction.

Thoracic Myelopathy Due to Gnathostomiasis Acquired in New Zealand

Gnathostomiasis is a zoonotic disease endemic in Asia. It most commonly manifests as gastrointestinal and cutaneous disease. Central nervous system involvement is a rare but feared complication, often leaving patients with permanent neurologic deficits. Clinicians outside of Asia and Latin America may have little experience with this illness, causing delays in diagnosis and treatment. We describe a 40-year-old woman who developed a progressive myelopathy over 18 months. She had never traveled outside of New Zealand. Cerebrospinal fluid (CSF) showed marked eosinophilia and Gnathostoma serology was positive in both serum and CSF. This is the first report of gnathostomiasis acquired in New Zealand, and the first case of neurognathostomiasis reported outside Asia. Clinicians should include neurognathostomiasis in the differential diagnosis of myelopathy and CSF eosinophilia, even if there is no history of travel to endemic areas.

Cerebral Sparganosis in Children: Epidemiologic and Radiologic Characteristics and Treatment Outcomes: A Report of 9 Cases

Pediatric cerebral sparganosis has been seldom reported. In the current study, we retrospectively reviewed the clinicopathologic records of 9 consecutive pediatric cases of cerebral sparganosis and analyzed their epidemiologic characteristics and clinical outcomes. Our cases included 6 boys and 3 girls, all from rural areas, and their median age at diagnosis was 9.4 (range, 5.8-12.9) years. The median duration of symptoms from onset to definite diagnosis was 21 months (range, 1 week to 3.7 years). Enzyme-linked immunosorbent assay revealed that serum anti-sparganosis antibody was positive in 9 of 9 patients and cerebrospinal fluid anti-sparganosis antibody was positive in 4 of 6 patients. Eight patients underwent craniotomy the removal of worms. The patients also received oral praziquantel. They were followed up for 2.2 years to 4.4 years. One patient died, and 8 patients survived. Three cases had poor outcomes whereas the outcome of the remaining 5 cases was satisfactory. Children are more at risk for sparganosis and cerebral sparganosis may be missed because of unclear epidemiologic history and nonspecific manifestations. Cerebrospinal fluid eosinophil counts and enzyme-linked immunosorbent assay for anti-sparganosis antibody and computed tomography/magnetic resonance imaging scans may be relied on for an early and accurate diagnosis before surgery.

Neurognathostomiasis in a young child in India: A case report

Eosinophilc meningitis is commonly associated with Angiostrongylus and Gnathostoma infection and has largely been reported from Thailand. We present the first case report of neurognathostomaisis in a pediatric patient from India. A 3.5year old girl presented with fever, parasthesis, behavioral changes followed by flaccid quadriparesis. Neuroimaging showed haemorrhagic radiculomyelitis with cerebrospinal fluid eosinophilia. Diagnosis of Gnathostoma infection was confirmed serologically and she was treated with anthelminthic drugs and steroids. This report emphasizes the increasing importance of central nervous system helminithic infections as an alternative diagnosis to common infections like neurotuberculosis in developing countries, even in pediatric patients. Increasing intercontinental travel and migration have increased the incidence and importance in the developed world as well.

A Rare Case of Ibuprofen-Induced Eosinophilic Meningitis in a 13-Year-Old Girl

Eosinophilic meningoencephalitis is based on clinical manifestations and microscopic identification of eosinophils present in cerebrospinal fluid (CSF). It is caused by a variety of helminthic infections with most common being angiostrongyliasis, gnathostomiasis, toxocariasis, cysticercosis, schistosomiasis, baylisascariasis, and paragonimiasis. Many case reports are there in which parasites have been found responsible, but there are rare reports of CSF eosinophilia associated with the use of drugs. We report a case of drug-induced (ibuprofen) eosinophilic meningitis in a healthy female who presented to us with severe headache and improved dramatically after drug withdrawal.

Cerebrospinal fluid eosinophilia is a sensitive and specific test for the diagnosis ofParelaphostrongylus tenuisin camelids in the northeastern United States

Aberrant migration of Parelaphostrongylus tenuis in camelids results in neurologic deficits, recumbency, and sometimes death. An antemortem diagnosis of P. tenuis in camelids is typically based upon the presence of characteristic asymmetric neurologic deficits, known exposure to white-tailed deer, cerebrospinal fluid (CSF) eosinophilia, and response to treatment. The diagnostic accuracy of CSF eosinophil percentage for the diagnosis of P. tenuis in camelids has not been critically examined. The objective of the current study was to determine the sensitivity (Se) and specificity (Sp) of CSF eosinophil percentage, CSF eosinophil concentration, total nucleated cell concentration, and protein concentration for the antemortem diagnosis of P. tenuis. Medical records of camelids admitted to Cornell University with clinical signs of neurologic disease, CSF analysis, and necropsy were examined from January 2000 through December 2009. Se and Sp were determined by receiver operating characteristic curves in camelids diagnosed with P. tenuis (n = 13) or other conditions (n = 24) based on postmortem examination. More than 17% of eosinophils in CSF had a Se of 85% and Sp of 92% for P. tenuis diagnosis (area under the curve [AUC]: 0.87; SE AUC: 0.07; P < 0.0001; 95% confidence interval [CI] AUC: 0.72-0.96), and >1.4 eosinophils/µl of CSF had a Se of 85% and Sp of 96% (AUC: 0.9; SE AUC: 0.06; P < 0.0001; 95% CI AUC: 0.76-0.97). Cerebrospinal fluid eosinophil percentage and concentration are sensitive and specific methods for diagnosing P. tenuis antemortem in camelids residing in regions endemic to white-tailed deer.

Idiopathic eosinophilic meningoencephalitis in a Dutch Warmblood gelding

SummaryAn increased content of eosinophils in cerebrospinal fluid (CSF) and eosinophilic infiltration of brain tissue are observed in eosinophilic meningoencephalitis (EME). After exclusion of various infectious diseases and further known causes of EME in other species, the diagnosis idiopathic EME was made at necropsy in the case reported here. To the authors' knowledge, this is the first report of idiopathic EME in a horse similar to the disorder occurring in dogs.

Good Outcome With Early Empiric Treatment of Neural Larva Migrans Due to Baylisascaris procyonis

We report a remarkably good outcome in a 14-month-old boy with early clinical diagnosis and aggressive empirical treatment of neural larva migrans caused by the raccoon roundworm Baylisascaris procyonis. He presented with fever, meningismus, lethargy, irritability and asymmetric spastic extremity weakness. Early findings of marked blood and cerebrospinal fluid eosinophilia and of diffuse white matter signal abnormality in the brain and spinal cord on MRI suggested a parasitic encephalomyelitis. Rapid presumptive treatment with albendazole and high-dose steroids halted progression of clinical signs. The diagnosis was confirmed by 2 sequential enzyme-linked immunosorbent assay studies positive for B procyonis serum immunoglobulin G and by Western blot. Field examination with soil sampling yielded infective Baylisascaris eggs. Repeat MRI 3 months later showed atrophy and diffuse, chronic white matter abnormalities, discordant with the marked clinical improvement in this interval. At 10 months, residual neurologic deficits included subtle paraparesis and moderate language delay. This case is the first in which spinal involvement in human Baylisascaris infection was clinically suspected and confirmed by neuroimaging. Importantly, early diagnosis and aggressive treatment of Baylisascaris meningo-encephalitis and myelitis with albendazole and high-dose steroids likely contributed to the good outcome in this patient, in contrast with previous reports.

脳脊髄液中にのみ好酸球増多をみとめた再発性脳脊髄炎の1例

We report a 30-year-old man with recurrent eosinophilic encephalomyelitis. He had a history of childhood asthma and allergic rhinitis. A half year before admission, when he suffered from a headache, a few lesions were indicated by brain MRI at another hospital. From a month before admission, he noticed gait disturbance, sensory impairment, difficulty in micturition, and constipation. Neurological examination revealed moderate muscle weakness in the feet, hypoesthesia below Th6, and bladder-bowel disturbance including impotence. Lumbar T(2) weigthed MRI showed a severe swelling and a hyperintense lesion at the conus medullaris. Brain MRI revealed several asymptomatic white matter lesions. Eosinophilia was documented in the cerebrospinal fluid (CSF) but not in the peripheral blood. Clinical symptoms and MRI findings were remarkably improved after steroid pulse therapy. Note that eosinophils in the CSF were also decreased after the treatment with apoptosis-like cells. We thought that CSF eosinophilia was the core pathogenic feature of this case, but clinical settings that provoke CSF eosinophilia such as parasites and other infectious agents, neuromyelitis optica, atopic myelitis, eosinophilic leukemia and hypereosinophilic syndrome could be ruled out. The remarkable responses to steroids without any additional therapy, compatible with idiopathic eosinophilic syndromes, confirmed that this was a case of idiopathic eosinophilic recurrent encephalomyelitis.

Diagnosis of Parelaphostrongylus spp. infection as a cause of meningomyelitis in calves

Migration of Parelaphostrongylus spp. has been documented to cause central nervous system damage in a number of aberrant host species but appears to be uncommon in cattle. The current report describes the clinical and laboratory findings, antemortem and definitive diagnosis, and response to treatment of Parelaphostrongylus spp. infection in five 3-7- month-old Limousin calves from 2 farms. All calves had signs of acute (n = 2) and chronic (n = 3) progressive spinal cord dysfunction. Cerebrospinal fluid analysis revealed a marked eosinophilic (acute cases) or lymphocytic (chronic cases) pleocytosis and elevated protein in all calves. A necropsy and histopathologic evaluation was performed on 2 euthanized calves, and histopathology revealed lymphoplasmacytic and eosinophilic meningomyelitis with multiple intradural and intramedullary expansile hyperplastic lymphoid nodules containing germinal centers and nematode fragments. DNA sequencing was performed on nested polymerase chain reaction products amplified with parasite-specific primers obtained from formalin-fixed and frozen spinal cord; PCR products from these 2 calves were 100% identical to Parelaphostrongylus species on DNA sequencing, confirming the diagnosis. Surviving calves rapidly improved following treatment with anthelmintics and corticosteroids. This case series identified Parelaphostrongylus spp. (likely P. tenuis) as a cause of spinal cord disease in calves and highlights the need for vigilance against aberrant parasite migration in calves grazing wet, snail-infested pastures. Cerebrospinal fluid eosinophilia is useful for supporting an antemortem diagnosis of Parelaphostrongylus in calves with acute neurologic disease; however, a lymphocytosis is observed in chronic or treated cases.

How Can Clinicians Ensure the Diagnosis of Meningitic Angiostrongyliasis?

Meningitic angiostrongyliasis (MA), caused by Angiostrongylus cantonensis, is often diagnosed by clinical criteria alone, because the confirmative serologic tests are not always available in the rural endemic areas. In this study, we evaluated the relationship between various clinical parameters of MA and the sero-positivity to sort out the predictive parameters to ensure the diagnosis. We enrolled consecutive adults in whom MA had been clinically diagnosed, who had serologic results for A. cantonensis, and negative serologic results for Gnathostoma spinigerum. There were 75 eligible patients; 26 (34.7%) and 49 (65.3%) patients who had negative and positive serologic tests for A. cantonensis, respectively. Baseline characteristics and laboratory results were comparable between sero-positive and -negative groups. Only the cerebrospinal fluid (CSF) eosinophil counts of 40% or higher was significantly predictive for positive serologic test with the adjusted odds ratio of 4.970 (95% confidence interval of 1.337-18.477). In diagnostic facilities in the endemic areas with the limited availability of serologic tests, clinicians can ensure the diagnosis of MA by using CSF eosinophil level.

Toxocara Canis Myelitis

Toxocara myelitis is a rare disease. Few cases have been reported in the literature. Patients present with myelopathy, occasional eosinophilia in blood and cerebrospinal fluid (CSF), with abnormal signals on magnetic resonance imaging (MRI). In the current study we report 17 cases of isolated Toxocara myelitis from a single tertiary referral center in Lebanon, with description of the clinical presentation, laboratory data, MRI findings, and response to antihelminthic treatment. Clinical and laboratory data were collected for 17 patients who presented with evidence of spinal cord disease. The clinical presentation included sensory, motor, and autonomic dysfunction, predominantly in the lower extremities. Patients exhibited a subacute or chronic course; this was either slowly progressive or remitting-relapsing with mild to moderate disability. The patients underwent extensive blood and CSF workup as well as MRI of the spinal cord and brain. Only 2 patients had a high eosinophil count in the CSF, although blood eosinophilia was seen in 6 patients. All patients tested positive for Toxocara canis antibodies in the blood and CSF. MRI of the spinal cord revealed a single characteristic lesion in the spinal cord with fusiform enlargement that was isointense on T1-weighted images and hyperintense on T2-weighted images. Nodular enhancement was seen after gadolinium injection. Treatment with albendazole, with or without steroids, resulted in marked neurologic improvement and normalization of the MRI in all patients.The finding of a single inflammatory MRI lesion in the spinal cord with positive Toxocara canis serology in the blood and CSF in cases of subacute or chronic myelitis suggests the diagnosis of Toxocara myelitis, irrespective of the presence of eosinophilia. Antihelminthic treatment is associated with a good outcome.

Ventriculoperitoneal shunt malfunction from cerebrospinal fluid eosinophilia in children: case-based update

Malfunction of cerebrospinal shunts is common and is due to multiple etiologies ranging from obstruction due to infiltrated brain tissue to mechanical disconnection. We review the differential diagnosis and recommended evaluation and treatment for cerebrospinal fluid (CSF) eosinophilia. We report a child who, following the use of an antibiotics-impregnated ventricular catheter, developed sterile ventriculoperitoneal shunt malfunction thought to be due to profound CSF eosinophilia. Following removal of the catheter, the eosinophilia spontaneously resolved, and at long-term follow up, the patient has a functioning non-antibiotic impregnated shunt catheter. Patients presenting with signs of shunt malfunction but without signs of CSF infection and with a raised CSF eosinophilia should be suspicious for cellular obstruction of their shunt system, i.e., sterile shunt malfunction.