ro13-9904 and Brain-Damage--Chronic

We describe unusual delayed recurrent episodes of ischemic stroke in a patient with initial good recovery from pneumococcal meningitis due to progressive arterial stenosis for over 3 months. We postulate that any of the following may have been responsible for his condition: widespread cerebral vasculopathy due to the effects of purulent material bathing the base of the brain, an immune-mediated para-infectious condition, or a rebound effect of the primary inflammatory reaction that was initially suppressed by dexamethasone. This case demonstrates that progressive arterial stenosis can evolve months after bacterial meningitis and should be recognized as a potential vascular complication.

Topics: Acetamides; Brain Damage, Chronic; Brain Ischemia; Ceftriaxone; Community-Acquired Infections; Constriction, Pathologic; Dexamethasone; Disease Progression; Drug Therapy, Combination; Humans; Linezolid; Male; Meningitis, Pneumococcal; Meropenem; Middle Aged; Oxazolidinones; Platelet Aggregation Inhibitors; Prednisolone; Recurrence; Thienamycins

Exacerbation of cerebrospinal fluid (CSF) inflammation in response to bacteriolysis by beta-lactam antibiotics contributes to brain damage and neurological sequelae in bacterial meningitis. Daptomycin, a nonlytic antibiotic acting on Gram-positive bacteria, lessens inflammation and brain injury compared to ceftriaxone. With a view to a clinical application for pediatric bacterial meningitis, we investigated the effect of combining daptomycin or rifampin with ceftriaxone in an infant rat pneumococcal meningitis model. Eleven-day-old Wistar rats with pneumococcal meningitis were randomized to treatment starting at 18 h after infection with (i) ceftriaxone (100 mg/kg of body weight, subcutaneously [s.c.], twice a day [b.i.d.]), (ii) daptomycin (10 mg/kg, s.c., daily) followed 15 min later by ceftriaxone, or (iii) rifampin (20 mg/kg, intraperitoneally [i.p.], b.i.d.) followed 15 min later by ceftriaxone. CSF was sampled at 6 and 22 h after the initiation of therapy and was assessed for concentrations of defined chemokines and cytokines. Brain damage was quantified by histomorphometry at 40 h after infection and hearing loss was assessed at 3 weeks after infection. Daptomycin plus ceftriaxone versus ceftriaxone significantly (P < 0.04) lowered CSF concentrations of monocyte chemoattractant protein 1 (MCP-1), MIP-1α, and interleukin 6 (IL-6) at 6 h and MIP-1α, IL-6, and IL-10 at 22 h after initiation of therapy, led to significantly (P < 0.01) less apoptosis, and significantly (P < 0.01) improved hearing capacity. While rifampin plus ceftriaxone versus ceftriaxone also led to lower CSF inflammation (P < 0.02 for IL-6 at 6 h), it had no significant effect on apoptosis and hearing capacity. Adjuvant daptomycin could therefore offer added benefits for the treatment of pediatric pneumococcal meningitis.

Topics: Animals; Anti-Bacterial Agents; Apoptosis; Brain Damage, Chronic; Ceftriaxone; Chemokines; Cytokines; Daptomycin; Drug Administration Schedule; Drug Therapy, Combination; Hearing Loss; Inflammation; Meningitis, Pneumococcal; Random Allocation; Rats; Rats, Wistar; Rifampin

We report a case of a 5-year-old boy with acute disseminated encephalomyelitis as the initial presentation of neuroborreliosis. Parents report an upper-airway infection a few days before the development of acute encephalopathy, mild facial palsy, and seizures. The patient needed mechanical ventilation for 10 days, and after extubation, he presented hypotonia, ataxia, dysarthria, as well as weak gag and cough reflexes. Brain magnetic resonance imaging showed hyperintense lesions on T2- and fluid-attenuated inversion recovery sequences on the right subcortical occipital and parietal region, left posterior arm of the internal capsule, and in the medulla oblongata. Borrelia burgdorferi was identified in the plasma and cerebrospinal fluid by polymerase chain reaction and in the plasma by Western blotting. He was treated with ceftriaxone, methylprednisolone, and human immunoglobulin. Recovery was partial.

Topics: Brain Damage, Chronic; Cefotaxime; Ceftriaxone; Child, Preschool; Coma; Diazepam; Encephalomyelitis, Acute Disseminated; Facial Paralysis; Humans; Immunoglobulins, Intravenous; Lyme Neuroborreliosis; Magnetic Resonance Imaging; Male; Mastoiditis; Methylprednisolone; Portugal; Respiration, Artificial; Respiratory Insufficiency; Respiratory Tract Infections; Seizures; Sinusitis; Vancomycin

Although more and more new potent antibiotics have been used, mortality and neurologic deficits still occur frequently following bacterial meningitis in children. In this article, the expression of brain-derived neurotrophic factor messenger ribonucleic acid (RNA) and its production in the brains of rats were investigated during the course of experimental bacterial meningitis and after treatment with an antibiotic plus dexamethasone. In the brains of Streptococcus pneumoniae-inoculated rats, brain-derived neurotrophic factor (BDNF) messenger RNA was obviously up-regulated after inoculation for 24 hours (P < .01) and then declined but was still greater than that in the brains of control rats after inoculation for 5 days (P < .05). The expression of brain-derived neurotrophic factor in the brains of infected rats treated by antibiotic was dose dependent, down-regulated, and almost undetectable (P < .01) but up-regulated after treatment with an antibiotic plus dexamethasone (P < .01). However, the expression of brain-derived neurotrophic factor messenger RNA did not change in control rats treated with an antibiotic. Brain-derived neurotrophic factor protein showed similar changes, except it declined to normal levels 5 days after inoculation. Brain-derived neurotrophic factor messenger RNA and its production were observed in some infiltrating inflammatory cells in the brain of infected rats. The results of our studies support the hypothesis that brain-derived neurotrophic factor might play a neuroprotective role in brain damage during bacterial meningitis, and the expression of brain-derived neurotrophic factor messenger RNA and its production might be inhibited after treatment with antibiotics. The findings suggest that both eradicating the bacterial pathogen with antibiotics and adjuvant administering of brain-derived neurotrophic factor might be more beneficial to prevent brain damage.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Brain; Brain Damage, Chronic; Brain-Derived Neurotrophic Factor; Ceftriaxone; Dexamethasone; Dose-Response Relationship, Drug; Drug Therapy, Combination; Gene Expression; Injections, Subcutaneous; Meningitis, Pneumococcal; Rats; Rats, Sprague-Dawley; RNA, Messenger

We have characterized the pattern of brain injury in a rat model of meningitis caused by group B streptococci (GBS). Infant rats (12-14 days old; n = 69) were infected intracisternally with 10 microliters of GBS (log10(2.3) to 4.5 colony-forming units). Twenty hours later, illness was assessed clinically and cerebrospinal fluid was cultured. Animals were either immediately euthanized for brain histopathology or treated with antibiotics and examined later. Early GBS meningitis was characterized clinically by severe obtundation and seizures, and histopathologically by acute inflammation in the subarachnoid space and ventricles, a vasculopathy characterized by vascular engorgement, and neuronal injury that was most prominent in the cortex and often followed a vascular pattern. Incidence of seizures, vasculopathy and neuronal injury correlated with the inoculum size (p < 0.01). Early injury was almost completely prevented by treatment with dexamethasone. Within days after meningitis, injured areas became well demarcated and showed new cellular infiltrates. Thirty days post-infection, brain weights of infected animals treated with antibiotics were decreased compared to uninfected controls (1.39 +/- 0.18 vs 1.64 +/- 0.1 g; p < 0.05). Thus, GBS meningitis in this model caused extensive cortical neuronal injury resembling severe neonatal meningitis in humans.

Topics: Animals; Animals, Newborn; Brain Damage, Chronic; Ceftriaxone; Cerebral Cortex; Cerebral Ventricles; Consciousness Disorders; Dexamethasone; Granulocytes; Meningitis, Bacterial; Neurons; Organ Size; Rats; Rats, Sprague-Dawley; Seizures; Severity of Illness Index; Streptococcal Infections; Streptococcus agalactiae; Subarachnoid Space; Vasculitis

During the ten-year period 1983-1992 40 children (16 girls and 24 boys) were treated for pyogenic meningitis caused by Haemophilus influenzae type b (Hib). The incidence was 1 case per year out of 5500 children younger than 6 years of age. The youngest child was 5.5 months old, 8 children (20%) were younger than 12 months. The highest incidence was during the second year of life (16 patients). The oldest patient was 11.5 years old. The course of Hib meningitis varied. The disease ran a fulminant course in 10 children. In 9 patients the symptoms evolved more gradually over a period of more than 48 hours, whereby 4 of these patients were only slightly ill on admission. Treatment until 1987 consisted of a combination of ampicillin and chloramphenicol, thereafter cetriaxon and ampicillin were used. Two patients died. One child was left with devastating handicaps and 5 children suffer from minor, but persisting sequelae (seizure disorder, delay in psychomotor development, attention deficit hyperactivity disorder, learning problems, speech delay). Transient disorders were found in 8 patients (EEG abnormalities, delay in psychomotor development, transient hearing problems). Severe hearing loss was seen in only one patient. 24 children (60% of all cases) recovered without any sequelae. Our results, in accordance with the literature, show that in spite of prompt availability of medical assistance, potent antibodies and a high standard of hospital care, the mortality and morbidity following Hib meningitis are still unacceptably high. Hence, we emphasize the need to eliminate Hib infection by immunization programmes.

Topics: Ampicillin; Brain Damage, Chronic; Ceftriaxone; Child; Child, Preschool; Chloramphenicol; Cross-Sectional Studies; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Incidence; Infant; Male; Meningitis, Haemophilus; Neurologic Examination