Miliary pattern of brain metastases - a case report of a hyperacute onset in a patient with malignant melanoma documented by magnetic resonance imaging.

BACKGROUND: Miliary brain metastases are a rare condition but associated with an exceedingly poor prognosis. We present the case of a patient suffering from malignant melanoma with an acute progressively worsening of neurological symptoms up to the loss of consciousness. The magnetic resonance imaging (MRI) demonstrated a new onset of disseminated, miliary spread of central nervous system metastases from a malignant melanoma within 4 days. CASE PRESENTATION: We report on a 57-year-old woman suffering from metastatic malignant melanoma positive for BRAF-V600E mutation who developed an acute onset of neurological symptoms. The patient received vemurafenib and dacarbacin as chemotherapeutic regime for treatment of malignant melanoma. After admission to our hospital due to progressive disturbance of memory and speech difficulty a magnetic resonance tomography (MRI) was performed. This showed no evidence of cerebral tumour manifestation. The symptoms progressed until a loss of consciousness occurred on day five after admission and the patient was admitted to our intensive care unit for orotracheal intubation. No evidence for infectious, metabolic or autoimmune cerebral disorders was found. Due to the inexplicable acute worsening of the neurological symptoms a second MRI was performed on day five. This revealed a new onset of innumerable contrast-enhancing miliary lesions, especially in the grey matter which was proven as metastases from malignant melanoma on histopathology. CONCLUSION: This case describes an unique hyperacute onset of tumour progression correlating with an acute deterioration of neurological symptoms in a patient suffering from miliary brain metastasis from BRAF positive malignant melanoma.

Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis.

Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. Additionally, SNPs in genes encoding complement pathway proteins have been linked to susceptibility to pneumococcal infection, although no associations with disease severity or outcome have been established. Here, we have performed a robust prospective nationwide genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. Consistent with these human data, C5a receptor-deficient mice with pneumococcal meningitis had lower CSF wbc counts and decreased brain damage compared with WT mice. Adjuvant treatment with C5-specific monoclonal antibodies prevented death in all mice with pneumococcal meningitis. Thus, our results suggest C5-specific monoclonal antibodies could be a promising new antiinflammatory adjuvant therapy for pneumococcal meningitis.

The chemokine CXCL13 in acute neuroborreliosis.

OBJECTIVE: Recent studies have suggested an important role of the B cell chemoattractant CXCL13 in acute neuroborreliosis (NB). Our aim was to confirm the diagnostic role of CXCL13 and to evaluate its relevance as a therapy response and disease activity marker in NB. METHODS: CXCL13 was measured in cerebrospinal fluid (CSF) and serum of patients with NB (n=28), systemic borreliosis (SB, n=9), Guillain-Barré syndrome (GBS, n=11), Bell's palsy (BP, n=19), other cranial nerve palsies (CNP, n=5), cephalgia (C, n=20), bacterial CNS infections (B-CNS-I, n=16) and viral CNS infections (V-CNS-I, n=18). For follow-up studies, serial sample pairs were evaluated from 25 patients with NB (n=56), 11 with B-CNS-I (n=25) and 14 with V-CNS-I (n=36). RESULTS: CSF-CXCL13 was significantly elevated in NB compared with other neurological diseases (p<0.001). Using receiver operating characteristic analysis, 337 ng/g was determined as a cut-off with a sensitivity of 96.4% and a specificity of 96.9%. Of all the parameters investigated, CSF CXCL13 showed the fastest response to antibiotic therapy, decreasing significantly (p=0.008) within 1 week. In untreated patients, CSF CXCL13 was elevated in patients with a short duration of disease. Borrelia burgdorferi antibody index showed no significant (p=0.356) change over follow-up. CONCLUSIONS: The study confirms the relevance of CXCL13 as a diagnostic biomarker of NB and suggests that CSF CXCL13 in NB is linked to duration of disease and could be a marker of disease activity and response to antibiotic therapy.

Severe meningoencephalitis caused by human herpesvirus 6 type B in an immunocompetent woman treated with ganciclovir.

Human herpesvirus 6 (HHV-6), the causative agent of exanthema subitum in childhood, can also induce meningoencephalitis in immunocompromised individuals. In contrast, HHV-6 encephalitis in immunocompetent patients is rare, and the clinical syndrome not well defined. We report a case of meningoencephalitis caused by HHV-6 type B in an otherwise healthy woman.

Discrepancies between brain CT imaging and severely raised intracranial pressure proven by ventriculostomy in adults with pneumococcal meningitis.

OBJECTIVES: Computed tomography (CT) of the brain is recommended for assessment of intracranial pressure (ICP) of patients with acute bacterial meningitis who are comatose or show focal neurological deficits. The aim of this report is to draw attention to the possibility of a discrepancy between CT findings and ICP values in some patients with pneumococcal meningitis. METHODS: We describe three adult patients with pneumococcal meningitis who had both successive CT examinations and ICP measurements at the time of clinically evident cerebral herniation (n = 2) and/or prolonged coma (n = 2). RESULTS: Although measurements with a ventriculostomy catheter indicated that all three patients had severely raised ICP values of 90, 44, and 45 mmHg, repeated cranial CT greatly underestimated true ICP values. Despite clinical evidence of acute cerebral herniation, it was not detected in the contemporary CT findings of two patients. Continuous ICP monitoring in the ICU helped to guide treatment for increased ICP; nevertheless, two patients died. CONCLUSIONS: The clinician must be aware that cranial CT may fail to rule out the possibility of severely raised ICP or cerebral herniation in a patient with pneumococcal meningitis. Therefore, ICP monitoring of patients with bacterial (especially pneumococcal) meningitis who are in prolonged coma should be considered early and regardless of the cranial CT appearances.

Experimental bacterial meningitis in rats: demonstration of hydrocephalus and meningeal enhancement by magnetic resonance imaging.

We investigated whether magnetic resonance imaging (MRI) is able to detect intracranial manifestations of advanced bacterial meningitis in rats. Meningitis was induced in nine animals by injecting 150 microl 10(7) colony forming units per ml of Streptococcus pneumoniae into the cisterna magna. MRI was performed 24 h (n = 5) and 48 h (n = 4) after infection. Controls included (I) animals that were injected intracisternally with 150 microl phosphate-buffered saline or (II) animals without puncture of the cisterna magna. T2-weighted and T1-weighted MR images before and after administration of 0.3 mmol kg(-1) of gadolinium-DTPA were obtained. Hydrocephalus was found in 7 of 9 infected animals, but not in the control group. Abnormal leptomeningeal enhancement was found in all infected animals, but in none of the controls. The animals imaged after 48 h showed a more pronounced hydrocephalus and a more intense leptomeningeal enhancement than animals imaged after 24 h. Even in small animals such as rats, MRI can be used to detect the presence of bacterial meningitis and its associated complications. MRI may be a useful noninvasive method for monitoring the possible effect of adjunctive therapeutic strategies in experimental studies of meningitis.