[Pneumococcal meningitis with accompanying severe hearing loss: 3D-FLAIR imaging of the inner ear and treatment].

A 66-year-old man was admitted to our hospital because of unconsciousness. He was diagnosed with pneumococcal meningitis and treated with a combination of antibiotics (meropenem hydrate), dexamethasone, and intravenous immunoglobulin. Although he gradually regained consciousness, he started showing signs of hearing disturbance. Measurement of auditory brainstem response revealed severe sensorineural hearing loss. The patient then underwent three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging, which revealed increased signals in the cochlea and the vestibuum, and their enhancement after gadolinium administration. This enhancement was still observed on images of the inner ear acquired on the 52nd hospital day. These findings suggested that the change of content in the lymph and the damage to the blood-labyrinth barrier was caused and aggravated by an immune response. Recent studies have shown that an MyD88-dependent immune response contributes to hearing loss in an experimental mouse model of pneumococcal meningitis. The patient was administered steroid pulse and hyperbaric oxygen therapies for improving the hearing deficit, but these therapies were discontinued because of the aggravation of hepatitis B and diabetes mellitus, which he had developed previously.

Sodium Butyrate Prevents Memory Impairment by Re-establishing BDNF and GDNF Expression in Experimental Pneumococcal Meningitis.

Pneumococcal meningitis is a serious infection of the central nervous system (CNS) with high fatality rates that causes reduced psychomotor performance, slight mental slowness, impairments in attention executive functions and learning and memory deficiencies. Previously, we demonstrated a correlation between memory impairment and decreased levels of brain-derived neurotropic factor (BDNF) in the hippocampi of rats subjected to pneumococcal meningitis. Emerging evidence demonstrates that histone acetylation regulates neurotrophins; therefore, a potential molecular intervention against cognitive impairment in bacterial meningitis may be the histone deacetylase (HDAC) inhibitor, sodium butyrate, which stimulates the acetylation of histones and increases BDNF expression. In this study, animals received either artificial cerebrospinal fluid as a placebo or a Streptococcus pneumoniae suspension at a concentration of 5 × 10(9) colony-forming units (CFU/mL). The animals received antibiotic treatment as usual and received saline or sodium butyrate as an adjuvant treatment. Ten days after, meningitis was induced; the animals were subjected to open-field habituation and the step-down inhibitory avoidance task. Immediately after these behavioural tasks, the animals were killed, and their hippocampi were removed to evaluate the expression of BDNF, nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). In the meningitis group that received saline, the animals presented memory impairment in both behavioural tasks, and hippocampal BDNF and GDNF expression was decreased. Sodium butyrate was able to prevent memory impairment and re-establish hippocampal neurotrophin expression in experimental pneumococcal meningitis.

Folic acid prevented cognitive impairment in experimental pneumococcal meningitis.

Streptococcus pneumoniae is a common cause of bacterial meningitis, with a high mortality rate and neurological sequelae. In contrast, folic acid plays an important role in neuroplasticity and the preservation of neuronal integrity. In the present study, we evaluated the influence of folic acid on memory, oxidative damage, enzymatic defence, and brain-derived neurotrophic factor (BDNF) expression in experimental pneumococcal meningitis. In animals that received folic acid at a dose of 10 or 50 mg, there was a reduction in both crossing and rearing during an open-field task compared with the training session, demonstrating habituation memory. During a step-down inhibitory avoidance task, there was a difference between the training and the test sessions, demonstrating aversive memory. In the hippocampus, BDNF expression decreased in the meningitis group; however, adjuvant treatment with 10 mg of folic acid increased BDNF expression, decreased lipid peroxidation, protein carbonylation, nitrate/nitrite levels, and myeloperoxidase activity and increased superoxide dismutase activity. In frontal cortex adjuvant treatment with 10 mg of folic acid decreased lipid peroxidation and protein carbonylation. There is substantial interest in the role of folic acid and related pathways in nervous system function and in folic acid's potential therapeutic effects. Here, adjuvant treatment with vitamin B9 prevented memory impairment in experimental pneumococcal meningitis.

Vitamin B6 prevents cognitive impairment in experimental pneumococcal meningitis.

Streptococcus pneumoniae is the relevant cause of bacterial meningitis, with a high-mortality rate and long-term neurological sequelae, affecting up to 50% of survivors. Pneumococcal compounds are pro-inflammatory mediators that induce an innate immune response and tryptophan degradation through the kynurenine pathway. Vitamin B6 acts as a cofactor at the active sites of enzymes that catalyze a great number of reactions involved in the metabolism of tryptophan, preventing the accumulation of neurotoxic intermediates. In the present study, we evaluated the effects of vitamin B6 on memory and on brain-derived neurotrophic factor (BDNF) expression in the brain of adult Wistar rats subjected to pneumococcal meningitis. The animals received either 10 µL of artificial cerebral spinal fluid (CSF) or an equivalent volume of S. pneumoniae suspension. The animals were divided into four groups: control, control treated with vitamin B6, meningitis, and meningitis treated with vitamin B6. Ten days after induction, the animals were subjected to behavioral tests: open-field task and step-down inhibitory avoidance task. In the open-field task, there was a significant reduction in both crossing and rearing in the control group, control/B6 group, and meningitis/B6 group compared with the training session, demonstrating habituation memory. However, the meningitis group showed no difference in motor and exploratory activity between training and test sessions, demonstrating memory impairment. In the step-down inhibitory avoidance task, there was a difference between training and test sessions in the control group, control/B6 group, and meningitis/B6 group, demonstrating aversive memory. In the meningitis group, there was no difference between training and test sessions, demonstrating impairment of aversive memory. In the hippocampus, BDNF expression decreased in the meningitis group when compared to the control group; however, adjuvant treatment with vitamin B6 increased BDNF expression in the meningitis group. Thus, vitamin B6 attenuated the memory impairment in animals subjected to pneumococcal meningitis.

[Implication of dexamethasone adjunctive therapy after the onset of cerebral vasculitis in Streptococcus pneumoniae meningitis]. / Implication du traitement adjuvant par dexaméthasone dans la survenue d'une artérite septique cérébrale au cours d'une méningite à Streptococcus pneumoniae.

Few adverse effects have been reported with adjunctive dexamethasone treatment in pneumococcal meningitis. Nevertheless, we report a case of cerebral vasculitis. A 49-year-old man was admitted for fever and altered mental status. Lumbar puncture revealed a high inflammatory response and Streptococcus pneumoniae was identified by culture. Antibacterial therapy and adjunctive dexamethasone treatment were initiated as recommended. The immediate outcome was favorable but due to the onset of focal cerebral abnormalities, a CT scan was performed on the ninth day showing cerebral vasculitis. The patient died on the thirteenth day despite antibacterial therapy and resuscitation. In our case, a secondary neurological worsening appeared when adjunctive dexamethasone treatment was stopped suggesting a rebound effect. Observation of similar cases may lead to modifying adjunctive dexamethasone treatment protocol in bacterial meningitis.

Meningitis-associated hearing loss: protection by adjunctive antioxidant therapy.

Hearing loss is the most frequent long-term complication of pneumococcal meningitis, affecting up to 40% of survivors. Unfortunately, adjuvant therapy with dexamethasone has failed to satisfactorily reduce its incidence. Therefore, we evaluated the use of antioxidants for the adjunctive therapy of meningitis-associated deafness. Eighteen hours after intracisternal injection of 7.5 x 10(5) colony-forming units of Streptococcus pneumoniae, rats were treated systemically either with ceftriaxone and the antioxidants and peroxynitrite scavengers Mn(III)tetrakis(4-benzoic acid)-porphyrin (MnTBAP) or N-acetyl-L-cysteine (NAC) or placebo (1 ml phosphate-buffered saline) for 4 days. Hearing was assessed by auditory brainstem response audiometry. Adjunctive antioxidant therapy significantly reduced the long-term hearing loss (14 days after infection) for square wave impulses (mean hearing loss +/- SD: ceftriaxone and placebo, 45+/-26 dB; ceftriaxone and MnTBAP, 9+/-23 dB; ceftriaxone and NAC, 19+/-30 dB) as well as 1 kHz (ceftriaxone and placebo, 28+/-19 dB; ceftriaxone and MnTBAP, 10+/-16 dB; ceftriaxone and NAC, 10+/-17 dB), and 10 kHz tone bursts (ceftriaxone and placebo, 62+/-27 dB; ceftriaxone and MnTBAP, 16+/-13 dB; ceftriaxone and NAC, 25+/-26 dB). Furthermore, both antioxidants attenuated the morphological correlates of meningogenic hearing loss, namely, long-term blood-labyrinth barrier disruption, spiral ganglion neuronal loss, and fibrous obliteration of the perilymphatic spaces. Adjuvant antioxidant therapy is highly otoprotective in meningitis and therefore is a promising future treatment option.

Pharmacologic interference with NF-kappaB activation attenuates central nervous system complications in experimental Pneumococcal meningitis.

This study assessed the effects of 2 different inhibitors of NF-kappaB activation on central nervous system complications and clinical symptoms in an advanced stage of experimental pneumococcal meningitis: the calpain inhibitor I N-acetyl-leucinyl-leucinyl-norleucinal (ALLN), which interferes with IkappaB proteolysis, and BAY 11-7085, which inhibits IkappaB phosphorylation. Pneumococcal meningitis was associated with an increase in NF-kappaB activity, as determined by immunohistochemistry and Western blot analysis of rat brains 24 h after infection. Treatment with ALLN or BAY 11-7085 improved the clinical scores of infected rats, compared with those of untreated infected rats. This beneficial effect was parallelled by a significant reduction of the increase in intracranial pressure, blood-brain barrier permeability (as measured by the Evans blue-extravasation technique), cerebrospinal fluid (CSF) pleocytosis, CSF interleukin-6 levels, and impairment of cerebrovascular CO(2) reactivity and autoregulation. Thus, pharmacologic interference with NF-kappaB activation might be a possible target for adjunctive therapy in bacterial meningitis.

[Respiratory aid using a diaphragmatic pacemaker in high paraplegia]. / Atemhilfe durch Zwerchfellschrittmacher bei hoher Querschnittslähmung.

Spastic tetraplegia due to cervical medullary injury above the origin of the phrenic nerve neurons means complete respiratory paralysis. In this case a phrenic pacemaker can be considered as an alternative to long term mechanical ventilation. An implantable 8-channel stimulation device has been developed for functional electrical stimulation of the phrenic nerves. The "Karussellstimulation" provides fatigue free stimulation for 24 hours a day. We report the case of a 12 year old girl with complete ventilatory insufficiency who underwent implantation of a phrenic pacemaker. 18 month after implantation she is independent of a conventional respirator and limits rehabilitation could be achieved. Electrophrenic respiration is of value in the rehabilitation management of tetraplegic patients with ventilatory insufficiency.

Effects of ampicillin and corticosteroids on brain water content, cerebrospinal fluid pressure, and cerebrospinal fluid lactate levels in experimental pneumococcal meningitis.

A study was made of the effects of antibiotics and corticosteroids on parameters that reflect brain dysfunction and potential neurological damage in experimental pneumococcal meningitis in rabbits. Brain water content was 398 +/- 10 g/100 g dry weight in normal rabbits and 410 +/- 11 g in rabbits after 24 hr of infection (P less than .001). Cerebrospinal fluid (CSF) lactate levels increased from 16.3 +/- 3.4 mg/dl to 69.5 +/- 28.2 mg/dl (P less than .001), and CSF pressure increased by +8.3 +/- 3.6 mm Hg (P less than .005) over the same interval. Antibiotic therapy with ampicillin sterilized CSF and normalized CSF pressure and brain water content in all animals within 24 hr, while CSF lactate levels remained elevated. Administration of methyl prednisolone, 30 mg/kg, or dexamethasone, 1 mg/kg, 15 and 22 hr after infection completely reversed the development of brain edema, but only dexamethasone also significantly reduced the increase in CSF lactate level (43.8 +/- 12.3 mg/dl) and CSF pressure (+1.8 +/- 2.7 mm Hg). Methyl prednisolone did not significantly affect pressure or lactate levels.