Bacterial cytolysin during meningitis disrupts the regulation of glutamate in the brain, leading to synaptic damage.

Streptococcus pneumoniae (pneumococcal) meningitis is a common bacterial infection of the brain. The cholesterol-dependent cytolysin pneumolysin represents a key factor, determining the neuropathogenic potential of the pneumococci. Here, we demonstrate selective synaptic loss within the superficial layers of the frontal neocortex of post-mortem brain samples from individuals with pneumococcal meningitis. A similar effect was observed in mice with pneumococcal meningitis only when the bacteria expressed the pore-forming cholesterol-dependent cytolysin pneumolysin. Exposure of acute mouse brain slices to only pore-competent pneumolysin at disease-relevant, non-lytic concentrations caused permanent dendritic swelling, dendritic spine elimination and synaptic loss. The NMDA glutamate receptor antagonists MK801 and D-AP5 reduced this pathology. Pneumolysin increased glutamate levels within the mouse brain slices. In mouse astrocytes, pneumolysin initiated the release of glutamate in a calcium-dependent manner. We propose that pneumolysin plays a significant synapto- and dendritotoxic role in pneumococcal meningitis by initiating glutamate release from astrocytes, leading to subsequent glutamate-dependent synaptic damage. We outline for the first time the occurrence of synaptic pathology in pneumococcal meningitis and demonstrate that a bacterial cytolysin can dysregulate the control of glutamate in the brain, inducing excitotoxic damage.

Fever and limp: thinking outside the box.

Fever and limp is a common presentation in the pediatric emergency department. We describe a case of a 21-month-old female patient with prolonged fever and difficulty bearing weight, ultimately diagnosed with a large intracranial abscess. Intracranial abscesses are a rare cause of limp and an uncommon diagnosis in pediatric patients without underlying congenital heart disease. This case highlights the importance of differentiating the features of limp secondary to pain from limp secondary to weakness, which is particularly difficult in the preschool-aged group. It is imperative for practitioners to consider disease of the central nervous system when evaluating acutely nonambulatory children with fevers.

[Cerebral trunk abscess due to Neisseria meningitidis in a 28-year-old immunocompetent patient]. / Abcès du tronc cérébral àNeisseria meningitidis chez une patiente de 28ans, immunocompétente.

Meningococcal disease can manifest in very different clinical situations. Meningococcal meningitis and fulminant meningococcemia (or purpura fulminans) are the most common forms of these infections, but many other manifestations can be seen including septic arthritis, pericarditis, pleurisy and conjunctivitis. Brain abscesses have also been described; they are a rare complication of meningococcal disease. We report the case of a 28-year-old immunocompetent patient who developed meningococcal infection associated with brain abscesses and oligo-arthritis.

Fonsecaea monophora cerebral phaeohyphomycosis: case report of successful surgical excision and voriconazole treatment and review.

We report a case of Fonsecaea monophora cerebral phaeohyphomycosis successfully treated with surgical excision and voriconazole monotherapy in a patient receiving maintenance immunosuppression therapy for 8 years after cadaveric renal transplantation. She presented with a severe frontal headache in the absence of any constitutional or neurologic symptoms. Brain magnetic resonance imaging showed an irregular 3.1 x 3.4 cm ring-enhancing lesion in her left frontal lobe. The patient underwent craniotomy and resection of her mass, with intraoperative spillage of some of her abscess contents into her lateral ventricle. Histopathology of her resected mass showed necrotic fragments of brain parenchyma with granulomatous inflammation and numerous pigmented fungal forms. A mold, recovered from cultures inoculated with portions of her brain resection specimen, was later definitively identified as Fonsecaea monophora. Initial serum (1-->3) beta-D-glucan (BG) levels exceeded 500 pg/ml. The patient received voriconazole, which she tolerated well, without recurrent headaches or abscess formation noted on serial brain imaging. Her BG declined to <31 pg/ml one year following her abscess resection. She discontinued antifungal therapy after an 18-month treatment course, and has remained free of any clinical or radiographic evidence of recurrent abscess formation three years later.

Meningitis and subgaleal, subdural, epidural empyema due to Pasteurella multocida.

Pasteurella is a Gram-negative coccobacillus found in 70-90% of oral cavities of cats, and as well, is isolated from the digestive systems of dogs, rats, rabbits, monkeys, and other animals. Pasteurella multocida has been known to cause infections in humans, the most familiar being soft tissue infection after animal bites. However, this organism may affect a variety of systems, causing serious disease. Pasteurella multocida can cause septic arthritis, osteomyelitis, pneumonia, endocarditis, meningitis, and septicemia. We report a case of bacterial meningitis, subgaleal, subdural, and epidural empyema due to Pasteurella multocida by a rabbit licking that resulted in neurological complications and a prolonged recovery period.

Integrative Transcriptome and Proteome Analyses Provide New Insights Into the Interaction Between Live Borrelia burgdorferi and Frontal Cortex Explants of the Rhesus Brain.

Borrelia burgdorferi (Bb), which is neurotropic, can attack the central nervous system (CNS), leading to the development of various neurologic symptoms. The pathogenesis of Lyme neuroborreliosis (LNB) remains poorly understood. Presently, there is a lack of knowledge of the changes in mRNA and proteins in the CNS following early disseminated Lyme disease. Explants from the frontal cortex of 3 rhesus brains were incubated with medium alone or with medium containing live Bb for 6, 12, or 24 hours. Then, we analyzed identified mRNA and proteins in the frontal cortex tissues, allowing for an in-depth view of the transcriptome and proteome for a macroscopic and unbiased understanding of early disseminated Lyme disease in the brain. Through bioinformatics analysis, a complex network of enriched pathways that were mobilized during the progression of Lyme spirochete infection was described. Furthermore, based on the analysis of omics data, translational regulation, glycosaminoglycan/proteoglycan-binding activity in colonization and dissemination to tissues, disease-associated genes, and synaptic function were enriched, which potentially play a role in pathogenesis during the interaction between frontal cortex tissues and spirochetes. These integrated omics results provide unbiased and comprehensive information for the further understanding of the molecular mechanisms of LNB.

Brain abscess formation within an endodermal cyst of the frontal lobe: case report.

A 38-year-old man with a right frontal lobe cyst was treated by endoscopic cystoventriculostomy in 1998. Cyst capsule histology revealed surprisingly an endodermal cyst. The patient was reoperated for cyst expansion by endoscopic re-cystoventriculostomy in 2005. In 2007, the patient suffered from brain abscess formation within the cyst which was punctured. The history was positive for a dental infection. In 2008, a recurrent brain abscess in the cyst occurred. The cyst was completely resected. There was no history of trauma or sinusitis. In all, endodermal cysts may mimic a paraxial arachnoid cyst. It may predispose for recurrent brain abscess formation - especially due to bacteraemia. This report confirms earlier presentations that endodermal cysts should be resected, and endoscopic cyst opening is not sufficient.

Cranial melioidosis presenting as a mass lesion or osteomyelitis.

OBJECT: Melioidosis is caused by Burkholderia pseudomallei and causes multiple abscesses in different organs of the body. Cranial melioidosis, although uncommon, is sometimes confused with tuberculosis and is therefore under-recognized. The authors report on 6 cases of cranial infections caused by Burkholderia pseudomallei, presenting as mass lesions or cranial osteomyelitis, and review the literature. METHODS: The authors performed a retrospective review of the records of patients with cranial melioidosis treated at their institution between 1998 and 2005 to determine the presentation, management, and outcome of patients with this infection. RESULTS: Of the 6 patients diagnosed with cranial melioidosis during this period, 4 had brain abscesses and 2 had cranial osteomyelitis. All patients were treated surgically, and a diagnosis was made on the basis of histopathological studies. All patients were started on antibiotic therapy following surgery and this was continued for 6 months. One patient died soon after stereotactic aspiration of a brain abscess, and the other 5 patients had good outcomes. CONCLUSIONS: Cranial melioidosis is probably more prevalent than has been previously reported. A high index of suspicion, early diagnosis, initiation of appropriate antibiotic therapy and treatment for an adequate period are essential for assuring good outcome in patients with cranial melioidosis. The authors recommend surgery followed by intravenous ceftazidime treatment for 6 weeks and oral cotrimoxazole for 6 months thereafter in patients with cranial melioidosis.

Meropenem-induced liver injury and beta-lactam cross-reactivity.

A 63-year-old man admitted to hospital for the management of a frontal lobe abscess developed elevated liver enzymes within 48 hours of receiving meropenem. Liver enzymes reached a maximum at 5 days postadministration of meropenem, with alanine aminotransferase 1160 U/L, aspartate aminotransferase 787 U/L, alkaline phosphatase 297 U/L and gamma-glutamyltransferase 252 U/L. Meropenem was ceased and liver function normalised. Meropenem was administered for a second time later in the patient's admission and again the patient developed rapidly increasing liver enzymes, with a mixed hepatocellular/cholestatic pattern. Other possible causes of liver injury were excluded following extensive investigations, and the patient's liver enzymes continued to normalise following meropenem discontinuation. The patient was asymptomatic during the admission and was transferred to a rehabilitation facility. This case demonstrates that meropenem can cause severe liver injury and that early recognition of drug-induced liver injury is important.

Neglected Recurrent Scalp Sinus: Calvarial Tuberculosis with Intracranial and Extracranial Extension.

BACKGROUND: Calvarial tuberculosis (TB) with intracranial tuberculoma and skin involvement is rare condition even in endemic regions. CASE PRESENTATION: A 43-year-old man presented with a generalized seizure, altered mental state, scalp swelling, and pus-discharging sinus over the scalp. Magnetic resonance imaging of the brain indicated a conflicting diagnosis of anaplastic meningiomas and chronic osteomyelitis with intracranial extension. Débridement and drainage of intracranial pus was performed. Histopathologic examination revealed TB. After surgery, the patient's general condition improved, and he was started on antitubercular drugs. CONCLUSIONS: Calvarial TB manifests with various clinical features, and strong clinical suspicion is needed to diagnose and treat it. Only a few cases of calvarial TB with either skin involvement or intracranial extension have been reported in the literature. The present case was challenging to diagnose with a rare presentation involving both intracranial and extracranial extension.

[Actinomycotic brain abscess in immunocompetent patient]. / Absceso cerebral actinomicótico en paciente inmunocompetente.

BACKGROUND: The actinomyces is germ commonly found in the normal flora of the oral cavity and gastro-intestinal and uro-genital tracts. Involvement in other locations is a very uncommon event. OBJECTIVES: To describe a patient with an actinomicotyc brain abscess CLINICAL CASE: We report the case of a patient who suffered a seizure and decreased level of consciousness. Imaging tests revealed the presence of lesions both in the lung and in the brain. An urgent craniotomy was performed and the diagnosis of actinomicotyc abscess was obtained. CONCLUSION: We describe the differential characteristics of this type of infection, discussing the diagnostic process and management in detail.

Isolation of Vibrio cholerae from the brain of a feedlot heifer with meningoencephalitis.

A 700-pound, 9-month-old Angus heifer from a feedlot presented with acute neurologic signs, characterized by circling, posterior weakness, and nonresponsiveness, followed by death. Histologically, the frontal lobe and the thalamus contained multiple foci of liquefaction that contained numerous degenerative neutrophils and foamy macrophages. Some of these foci were centered on blood vessels that contained fibrin thrombi and exhibited varying degrees of fibrinoid necrosis of the vessel wall. There was adjacent axonal degeneration and neuronal necrosis characterized by pronounced cytoplasmic eosinophilia, peripheralization of the nuclei, and loss of Nissl substance. Aerobic culture of the brain yielded moderate growth of Vibrio species, which was determined to be Vibrio cholerae by polymerase chain reaction analysis of a 438-base pair fragment of the 16 S ribosomal RNA gene. V. cholerae are motile, gram-negative, curved rod-shaped bacteria. Some strains of V. cholerae are important food- and water-borne bacterial pathogens that produce an often fatal diarrhea in humans. This is the first known case report of V. cholerae meningoencephalitis and cerebral abscessation in a bovine.

Giant subdural empyema in a child: a case report.

An unusual case of a giant (8 x 6 x 6 cm) frontoparietal SDE of Streptococcus pneumoniae in a 17-month-old child is reported. The initial diagnosis was made with emergency CT. The purulent material was removed via a frontoparietal craniotomy. A series of postoperative MR imaging showed the gradual reduction in size of the lesion, although collapsed capsule, fibrous thickening of meningeal structures and associated displacement of the underlying brain persisted. The child was symptom-free in a follow-up period of 15 months. This case showed that SDE may reach a giant size and thus may mimic an intra-axial lesion; the coronal MR imaging is a more reliable diagnostic tool than the emergency axial CT in giant SDE of upper convexity localization, and the clinical improvement may be more impressive than the radiological changes.

Intracranial tuberculomas: the Hofuf, Saudi Arabia experience.

Tuberculosis usually involves the brain through haematogenous spread. The mass lesion caused by tuberculosis in the brain is called tuberculoma, which is a conglomerate of tubercles. Tuberculomas may also be found in the spinal cord. Because of their slow growth they often become calcified. The study was conducted at the King Fahad Hospital, Hofuf, Al Hassia, Saudi Arabia between 1992 and 1998. It was a prospective study of all patients which had intracrainal mass lesions which showed typical ring-enhancement on brain CT scan with contrast. Twenty patients satisfied inclusion into the study. Of the 20 patients studied, 19 (95%) were males and 1 (5%) was a female. The ages ranged between 22 and 50 years. Eighteen (90%) of the patients were immigrant labourers from Asia and 2 (10%) were Saudi nationals, a male aged 50 years and a female aged 22 years. Fifteen (83.5%) were from India, 2 (11.1%) from Bangladesh, and 1 (5.6%) from Sri Lanka. The presenting feature in 60% of cases was focal seizure with secondary generalisation. 20% had primary generalized seizures, and 30% presented with headache, 25% with weakness of the limbs, 15% with fever and 10% each with vomitting and blurred vision, respectively. In 65% of cases, there was noneurological deficit but 35% had pyramidal weakness in the limbs. In 55% of cases the Tuberculomas were located in the left cerebral hemisphere. 30% in the right cerebral hemisphere and in 15%, the lesions were in both hemisphere. When a male Asian immigrant labourer aged between 20 and 40 years presents with seizures with or without headache, he should have a brain CT scan with contrast to exclude intracranial Tuberculoma. A short course of anti-tuberculous therapy may be tried where there is doubt, irrespective of normal erythrocyte sedimentation rate (ESR). We suggest that when the presenting symptom is primary generalized tonic clonic seizure, the intracranial Tuberculoma is located in the frontal lobe: a high erythrocyte sedimentation rate (ESR) may indicate multiple Tuberculomas.

Giant osteoma of the frontoethmoidal sinus associated with two cerebral abscesses.

A 36-year-old woman presented with severe frontal headache, fever, left palpebral swelling, and proptosis. Radiographic studies showed a giant frontoethmoidal osteoma, that extended intracranially into the frontal lobe and was associated with two abscesses, one within the lesion and the other in the right frontal lobe. The tumour was excised and the abscesses drained. The patient made a full recovery.