Cerebral Granuloma Research Articles

A Salmonella Pullorum outbreak with neurological signs in adult layers and outbreak investigation using whole genome sequencing

ABSTRACT This report describes a Salmonella enterica subspecies enterica Serovar Gallinarum Biovar Pullorum (SP) outbreak in a Dutch laying flock of 65 weeks of age (W) showing increased mortality, decreased egg production, and neurological signs. The flock was vaccinated three times with a live S. enteritis and S. typhimurium vaccine in the rearing period. At 71 W, as mortality peaked, a live SG 9R vaccine was applied. At 76 W, mortality decreased and egg production stabilized but did not return to a normal level. Post-mortem, histological, bacteriological, and serological examinations were frequently performed. Gross findings in diseased and dead birds were characterized by hepatomegaly, splenomegaly, and oophoritis. SP was frequently isolated from the liver, spleen, ovary, and bone marrow, and the isolation rate did not vary significantly between the different organs. In birds with neurological signs, histological examination and immunostaining showed cerebral granulomas in the presence of Salmonella. Previous Salmonella vaccinations did not hamper the detection of specific SP antibodies (positive at serum dilution ≥ 1:8) using a commercial rapid plate agglutination test. At 85 W, 40 clinically healthy birds were investigated and three had ovarian lesions, explaining egg production not returning to normal. These birds had antibodies against SP, indicating contact with the bacterium, but carrier status could not be confirmed by culture. Phylogenetic analysis showed SP isolates within this outbreak to be clonal and differing from SP isolates from previous outbreaks. RESEARCH HIGHLIGHTS Cerebral granulomas are associated with nervous signs in Salmonella Pullorum outbreak. Bone marrow is also a recommended tissue for isolation of Salmonella Pullorum. Rapid plate agglutination test detects Pullorum antibodies in a vaccinated flock. Phylogenetic analysis showed clonality of isolates within the outbreak.

Central nervous system manifestations of LRBA deficiency: case report of two siblings and literature review

BackgroundLPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency disease (PID) characterized by a regulatory T cell defect resulting in immune dysregulation and autoimmunity. We present two siblings born to consanguineous parents of North African descent with LRBA deficiency and central nervous system (CNS) manifestations. As no concise overview of these manifestations is available in literature, we compared our patient’s presentation with a reviewed synthesis of the available literature.Case presentationsThe younger brother presented with enteropathy at age 1.5 years, and subsequently developed Evans syndrome and diabetes mellitus. These autoimmune manifestations led to the genetic diagnosis of LRBA deficiency through whole exome sequencing with PID gene panel. At 11 years old, he had two tonic–clonic seizures. Brain MRI showed multiple FLAIR-hyperintense lesions and a T2-hyperintense lesion of the cervical medulla. His sister presented with immune cytopenia at age 9 years, and developed diffuse lymphadenopathy and interstitial lung disease. Genetic testing confirmed the same mutation as her brother. At age 13 years, a brain MRI showed multiple T2-FLAIR-hyperintense lesions. She received an allogeneic hematopoietic stem cell transplantation (allo-HSCT) 3 months later. Follow-up MRI showed regression of these lesions.ConclusionsNeurological disease is documented in up to 25% of patients with LRBA deficiency. Manifestations range from cerebral granulomas to acute disseminating encephalomyelitis, but detailed descriptions of neurological and imaging phenotypes are lacking. LRBA deficiency amongst other PIDs should be part of the differential diagnosis in patients with inflammatory brain lesions. We strongly advocate for a more detailed description of CNS manifestations in patients with LRBA deficiency, when possible with MR imaging. This will aid clinical decision concerning both anti-infectious and anti-inflammatory therapy and in considering the indication for allo-HSCT.

Distribution of M1 and M2 macrophages in cerebral granulomas caused by Encephalitozoon cuniculi

Encephalitozoon cuniculi spores cause severe granulomatous inflammation in the brain where mononuclear cells and macrophages infiltrate. Here, we orally infected New Zealand white rabbits with 1 × 106E. cuniculi viable spores to study the recruitment and localization of macrophages in brain granulomas. At day 30 post-infection, the positive phenotype markers iNOS (M1) and Arg-1 (M2) were located in the periphery and center of granulomas, respectively. Live intracytoplasmic spores were found only in positive Arg-1 cells. This is the first work to describe the recruitment and distribution of M1 and M2 macrophages in the brain granulomas of rabbits infected with E. cuniculi.

Case Report: Multiple Schistosomiasis Japonica Cerebral Granulomas without Gastrointestinal System Involvement: Report of Two Cases and Review of Literature.

Most schistosomiasis japonica cerebral granulomas reported in the literature have been single and located in the cerebellum, and multiple lesions located in the cerebral hemisphere are uncommon and often misdiagnosed as metastases or gliomas. We describe two rare cases of multiple schistosomiasis japonica cerebral granulomas. Laboratory examinations and cerebrospinal fluid were normal. Parasite eggs were not detected in the stool. No positive findings were detected in the abdominal ultrasonography or chest radiography. Magnetic resonance revealed two intensive patchy lesions in the cerebral hemisphere and surrounded by a large area of edema in both of our patients. Both were misdiagnosed as glioma or metastatic carcinoma before operation. Pathological examination confirmed that the diagnosis was schistosomiasis japonica cerebral granuloma. Praziquantel and dexamethasone were administered. Both patients are alive, symptom-free, and without evidence of recurrence. Combining our date with other literature reports, we summarize the possible mechanism, reasons for misdiagnosis, radiological characteristics, surgical treatment, and postoperative management of schistosomiasis japonica cerebral granuloma, which can be used for clinical reference and to improve our knowledge of schistosomiasis japonica cerebral granuloma.

Opportunistic neuroinfections in retroviral disease - retrospective hospital-based study from india

Background: Patients with retroviral disease are prone for opportunistic infections which are significant cause of mortality and morbidity. Cryptococcosis, tuberculosis and toxoplasma are the commonest infections occurring at all stages of the disease. Objective: This study was undertaken to evaluate the pattern of opportunistic infections and in hospital mortality in AIDS patients. Methods: This retrospective analysis was done in tertiary care hospital from 2001-2014 services. Details of clinical profile and laboratory investigations of patients admitted under neurological services with neuroinfections were studied. Results: There were 167 patients with 131 men and 36 women (ratio 3.63:1). Their age ranged from 16 to 67 years (39.25 ± 8.85). Clinical presentation was acute in 58%, subacute in 32% and chronic in 10%. Fever (65.86%) and headache (86.82%) were common symptoms. Seizures were present in 25% of the patients and altered sensorium in 37%. Among the neuroinfections cryptococcal meningitis was the commonest etiology accounting for 40%. Other infections included tuberculosis (19%), viral (20)%, mixed tubercular and fungal (13%) and toxoplasmosis (6%). PML was seen in 10%. Dyselectrolemia was seen in 16.76% patients. Fifteen patients died during admission (9%) . Twenty patients had cerebral granulomas. Mortality was the highest in cryptococcal meningitis (46.6%) followed mixed infection (26.6%), neurotuberculosis (13.3%) and viral etiology (13.3%). Complication at the onset and during the course consisted of renal dysfunction in 19, uncontrolled seizures in 16 patients, and hepatic dysfunction in 11 patients. Conclusion: Commonest opportunistic infection in AIDS patients is cryptococcal meningitis. Others being neurotuberculosis, progressive multifocal leucoencephalopathy and toxoplasmosis.

Striated Enhancement Sign in Invasive Cerebral Fungal Granuloma by Aspergillus: a Case Report

A 21-year-old man came to us from the local hospital with intermittent headache and vomiting lasting for 10 days. The patient did have no fever and immunocompromised history. Clinical examination showed that the patient suffered from superficial coma, disappearment of light reflex of the left eye, and the weakness of the right extremity. MR imaging of the brain was performed to determine the cause of headache and vomitting. Chest computed tomography (CT) was performed to check for the lung disorder. The chest CT examination was normal. MR images showed a mass lesion in the left frontal lobe involved corpus callosum and left basal ganglia region. The lesion showed slight hyperintensity on T2-weighted imaging and slight hypointensity on T1-weighted imaging, and patchy hyperintensity on diffusion weighted imaging (Fig. 1). After contrast administration, the lesion showed striated enhancement sign (radiating linear enhancement) (Fig. 2). The white blood cell count in peripheral blood was 9.67×10/L, and that in cerebrospinal fluid was negative. The patient underwent a brain operation, and the hyphae of aspergillus were observed on the pathological section (Fig. 3).

Computational modeling of tuberculous meningitis reveals an important role for tumor necrosis [formula omitted

Tuberculosis is a global health issue with annually about 1.5 million deaths and 2 billion infected people worldwide. Extra-pulmonary tuberculosis comprises 13% of all cases of which tuberculous meningitis is the most severe. It has a high mortality and is often diagnosed once irreversible neurological damage has already occurred. Development of diagnostic and treatment strategies requires a thorough understanding of the pathogenesis of tuberculous meningitis. This disease is characterized by the formation of a cerebral granuloma, which is a collection of immune cells that attempt to immunologically restrain, and physically contain bacteria. The cytokine tumor necrosis factor-α is known for its important role in granuloma formation. Because traditional experimental animal studies exploring tuberculous meningitis are difficult and expensive, another approach is needed to begin to address this important and significant disease outcome. Here, we present an in silico model capturing the unique immunological environment of the brain that allows us to study the key mechanisms driving granuloma formation in time. Uncertainty and sensitivity analysis reveals a dose-dependent effect of tumor necrosis factor-α on bacterial load and immune cell numbers thereby influencing the onset of tuberculous meningitis. Insufficient levels result in bacterial overgrowth, whereas high levels lead to uncontrolled inflammation being detrimental to the host. These findings have important implications for the development of immuno-modulating treatment strategies for tuberculous meningitis.

Life-threatening disseminated tuberculosis as a complication of TNF-α blockade in an adolescent

Life-threatening disseminated tuberculosis developed in a 17-year-old girl who was treated with the TNF-α blocker adalimumab for refractory SAPHO syndrome. The patient presented to the emergency department with dyspnea and somnolence and within 2 h developed the clinical picture of a septic shock. In addition to this unusual presentation, she showed a complicated course with increasing cerebral granuloma formation in spite of adequate antimycobacterial treatment. Immune reconstitution after discontinuation of TNF blockade may contribute to this "paradoxical reaction." Possible implications for screening, diagnosis, and treatment of tuberculosis in children and adolescents receiving anti-TNF treatment are discussed.

Cerebral Xanthoma in a Long-nosed Snake (Rhinocheilus lecontei)

ABSTRACT A case of cerebral xanthomatosis is described in a long-nosed snake (Rhinocheilus lecontei). A 13-year-old long-nosed snake presented for pronounced lethargy, anorexia, and diminished righting reflex. The snake failed to respond to medical therapy and was euthanized. On histology, a focal cerebral cholesterol granuloma (xanthoma) was found within the lateral ventricle causing mild hydrocephalus, marked compression atrophy of the overlying dorsal cortex, and mild compression and disorganization of the ventral nucleus sphericus. Xanthomatosis is believed to be the cause of the neurological signs and the ultimate lack of response to medical therapy in this case. This case demonstrates another differential for neurologic dysfunction in snakes.

Encephalitozoonosis in pet rabbits (Oryctolagus cuniculus): pathohistological findings in animals with latent infection versus clinical manifestation

Encephalitozoon cuniculi is a common infectious agent of rabbits. The aim of this study was to determine the distribution and extent of histological lesions in the brain and in the kidney of naturally infected pet rabbits with or without clinical encephalitozoonosis. In 71 animals (33 with symptoms) which died or were euthanised, histopathological examination including staining of spores (Ziehl-Neelsen, acid-fast trichrome) was performed and changes were described quantitatively. The cerebrum was the most frequently affected brain region (97.5%), whilst the cerebellum (55%) and the vestibular cores (37.5%) were less commonly concerned. Granulomas were found in 77.5% of animals with encephalitis and in 12.5% of rabbits with interstitial nephritis. Although cerebral granulomas were found irrespective of the grade of histological changes, they were significantly correlated with changes at higher grades. There was no correlation between the severity of encephalitis and neurological symptoms. Since severe lesions were also found in clinically inconspicuous animals, histological findings of inflammatory lesions are not indicative of overt encephalitozoonosis as the causative agent for neurological signs. Other diseases causing neurological symptoms, such as suppurative encephalitis, otitis media as well as malignant lymphoma were also detected in the rabbit population that was examined in the present study.

Clinical and pathological diagnosis of cerebral schistosomal granuloma

目的 对脑型血吸虫病肉芽肿的临床和病理诊断进行分析.方法 将患者手术中切除的脑部病变组织,采用快速或常规石蜡包埋切片,HE染色,显微镜下观察脑血吸虫病肉芽肿的病理形态.结果 组织切片中见血吸虫病肉芽肿,急性期,中央为新鲜虫卵肉芽肿,周围大量嗜酸性粒细胞浸润,形成嗜酸性肉芽肿.慢性期为退变虫卵,其外为增生的胶质细胞,上皮样细胞和异物巨细胞,形成假结核样结节,以及纤维组织增生、胶元化.结论 血吸虫病肉芽肿是脑型血吸虫病临床表现的病理基础,以血吸虫卵为中心形成的肉芽肿病变,是脑型血吸虫病的主要病理学形态特点。

Tuberculous meningoencephalitis in a pregnant woman presenting 7 years after removal of a cerebral granuloma

We describe the unusual case of a young woman with a history of seizures and a granulomatous, likely tuberculous brain lesion that was surgically removed. She had an uneventful recovery without any additional therapy other than anti-epileptics. Seven years later, she presented during pregnancy with culture-confirmed tuberculous meningoencephalitis. This case highlights the spectrum of tuberculous central nervous system disease and the challenges in diagnosis.

Surgical Treatment of Epilepsy with Chronic Cerebral Granuloma Caused by Schistosoma japonicum

To study the surgical treatment of epilepsy with cerebral granuloma caused by Schistosoma japonicum. Two hundred fifty cases of epilepsy caused by cerebral schistosomiasis from 1955 to 2004 were analyzed retrospectively. There were no deaths. Follow-up of 196 cases for 4-5 years after operation demonstrated that 180 cases (92%) were seizure-free or well-controlled. Surgical treatment should be considered when drug therapy fails to control epilepsy or the lesion shows mass effect. Intraoperative electrocorticography monitoring is helpful to define the extent of the resection of the lesion.

Elevated relapse rate under oral methotrexate versus leflunomide for maintenance of remission in Wegener's granulomatosis

Results from open-label trials suggest that methotrexate (MTX) and leflunomide (LEF) are effective for maintenance of remission in Wegener's granulomatosis (WG), but data from randomized controlled clinical trails are not yet available. In this multicentre, prospective randomized controlled clinical trial, patients with generalized WG were treated either with oral LEF 30 mg/day or oral MTX (starting with 7.5 mg/week reaching 20 mg/week after 8 weeks) for 2 yrs following induction of remission with cyclophosphamide. The primary endpoint was the incidence of relapses. Secondary outcome parameters were DEI, BVAS, SF-36, cANCA-titre, ESR and CRP. Fifty-four patients were included in the study, 26 in the LEF-limb, 28 in the MTX-limb. In the LEF-group, six patients relapsed after a median time of 7 months, thereof one major relapse with a new pulmonary manifestation. In the MTX-group, 13 relapses occurred in 6 months, of which seven were major: rapidly progressive glomerulonephritis (n = 4), pulmonary haemorrhage (n = 2) and one cerebral granuloma. The significantly higher incidence of major relapses in the MTX-limb (P = 0.037) led to premature termination of the study. In the LEF-limb, four patients were withdrawn due to hypertension (n = 2), peripheral neuropathy (n = 1) and leucopenia (n = 1). LEF at a dosage of 30 mg/day appears to be effective in the prevention of major relapses in WG, however, this is associated with an increased frequency of adverse events. Further studies testing other dosing regimens of lower doses of LEF are needed to confirm these promising results in larger patients cohorts.

Successful unrelated bone marrow transplantation in a child with chronic granulomatous disease complicated by pulmonary and cerebral granuloma formation

We report on a 6-year-old boy with chronic granulomatous disease (CGD) complicated by chronic inflammatory reactions with formation of large pulmonary granuloma as well as intracerebral lesions. Bone marrow transplantation (BMT) from an unrelated donor led to stable reconstitution, to rapid resolution of pulmonary granuloma, and to rapid resolution of intracerebral lesions.

Short-Term Antiepileptic Treatment of Solitary Cerebral Cysticercosis

A prospective randomized study of short-term vs long-term antiepileptic drug (AED) treatment of 206 subjects with new onset seizures and solitary cerebral cysticercus granuloma (SCCG) was conducted at the Department of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

Tuberculosis and diffusion MR imaging and spectroscopy

Central nervous system tuberculosis remains a major problem in developing countries, where an increasing incidence can be seen among immunocompromised patients. Cerebral tubercular granulomas with central necrosis are usually seen as rim-enhancing lesions on magnetic resonance imaging (MRI), and on T2weighted images the center may be of variable signal intensity. The time it takes to obtain a diffusionweighted image (DWI) is short, and in many institutions it is a routine part of any MRI of the brain. DWI MRI has revolutionized the imaging of acute infarction in the brain. The value of DWI in cerebral infections and in the differentiation of abscesses from necrotic tumors has been widely reported. Yet, little has been written about DWI on tubercular lesions. Medical journals publish positive results, but radiologists should also be familiar with the limitations of modern imaging techniques. In this issue of Acta Radiologica, Drs Arun Batra and Brig R. P. Tripathi present their experience on diffusion MRI and MR spectroscopy in the evaluation of focal tubercular lesions. This is so far the largest material on this topic and it shows that DWI and MR spectroscopy help in determining the nature of tubercular lesions; however, since the findings vary, they do not help in specific characterization. This article is highly recommended reading.

Two autopsy cases of multiple cerebral tuberculomas

Two cases of multiple cerebral tuberculomas are described. A 59‐year‐old female had liver cirrhosis and was suspected of having metastatic tumors in the brain. A 65‐year‐old female had chronic renal failure and was diagnosed with miliary tuberculosis and treated with antituberculous drugs. In both cases, consciousness became disturbed gradually. Both patients were diagnosed with multiple cerebral tuberculomas after death. Histologically, both cases showed cerebral granulomas comprising epithelioid cells mixed with reactive astrocytes, and fibrous gliosis surrounding a core of caseous necrosis. These lesions were readily detected by Holzer staining. Some blood vessels around the granulomas showed vasculitis with lymphocyte infiltration in the walls and obliteration of the lumina by epithelioid cell proliferation. In this report, the unique histological features of the multiple cerebral tuberculoma are described and it is suggested that the obliterative vasculitis around them may have caused the disturbed consciousness.

Comparative study of CT and MRI in patients with seizures and a solitary cerebral cysticercus granuloma

Comparative study of CT and MRI in patients with seizures and a solitary cerebral cysticercus granuloma

Cerebral granuloma and meningitis caused by Candida albicans

The authors report the case of a previously healthy patient who had recurrent cerebral granulomas and meningitis caused by Candida albicans 15 years after the first onset. A combination of external drainage of cerebrospinal fluid (CSF) and intraventricular and intravenous chemotherapy with antifungal agents resulted in a favorable outcome. Investigation of this patient revealed no immunological dysfunction, lymphoproliferative disorder, or candidicidal defect of peripheral blood leukocytes. Sequential measurement of Candida mannan antigen in CSF was useful for establishing the early diagnosis of cerebral candidiasis and for judging the effect of our antifungal chemotherapy. In determining the surgical indications and timing of placement of a ventriculoperitoneal or ventriculoatrial shunt for meningitis subsequent to hydrocephalus after candidal infection, it is better to confirm normal concentrations of the mannan antigen in the CSF repeatedly for more than a week and to determine that cultures of the CSF are negative for Candida albicans.