Phase I trial of intrathecal liposomal cytarabine in children with neoplastic meningitis.
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PURPOSE: We performed a phase I trial of intrathecal (IT) liposomal cytarabine (DepoCyt; Enzon Pharmaceuticals, Piscataway, NJ and SkyePharma Inc, San Diego, CA) to determine the maximum-tolerated dose, the dose-limiting toxicities, and the plasma and CSF pharmacokinetics of IT lipsomal cytarabine in children >/= 3 years of age with advanced meningeal malignancies. PATIENTS AND METHODS: Eighteen assessable patients received IT liposomal cytarabine through either an indwelling ventricular access device or via lumbar puncture. Liposomal cytarabine was given once every 2 weeks during induction, once every 4 weeks during consolidation, and once every 8 weeks during the maintenance phase of treatment. The initial dose was 25 mg, with subsequent escalations to 35 and 50 mg. CSF pharmacokinetic samples were obtained in a subset of patients. RESULTS: Arachnoiditis, characterized by fever, headache, nausea, vomiting, and back pain was noted in the first two patients at the 25 mg dose level. Therefore, subsequent patients were treated with dexamethasone, beginning the day of liposomal cytarabine administration and continuing for 5 days. Headache (grade 3) was dose limiting in two of eight patients enrolled at the 50 mg dose level. Eight of the 14 patients assessable for response demonstrated evidence of benefit manifest as prolonged disease stabilization or response. CONCLUSION: The maximum-tolerated dose and recommended phase II dose of liposomal cytarabine in patients between the ages of 3 and 21 years is 35 mg, administered with dexamethasone (0.15 mg/kg/dose, twice a day for 5 days). A phase II trial of IT liposomal cytarabine in children with CNS leukemia in second or higher relapse is in development. (+info)
An unusual case of chronic meningitis.
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BACKGROUND: Chronic meningitis is defined as symptoms and signs of meningeal inflammation and persisting cerebrospinal fluid abnormalities such as elevated protein level and pleocytosis for at least one month. CASE PRESENTATION: A 62-year-old woman, of unremarkable past medical history, was admitted to hospital for investigation of a four-week history of vomiting, malaise an associated hyponatraemia. She had a low-grade pyrexia with normal inflammatory markers. A CT brain was unremarkable and a contrast MRI brain revealed sub-acute infarction of the right frontal cortex but with no evidence of meningeal enhancement. Due to increasing confusion and patient clinical deterioration a lumbar puncture was performed at 17 days post admission. This revealed gram-negative coccobacilli in the CSF, which was identified as Neisseria meningitidis group B. The patient made a dramatic recovery with high-dose intravenous ceftriaxone antibiotic therapy for meningococcal meningitis. CONCLUSIONS: 1) Chronic bacterial meningitis may present highly atypically, particularly in the older adult. 2) There may be an absent or reduced febrile response, without a rise in inflammatory markers, despite a very unwell patient. 3) Early lumbar puncture is to be encouraged as it is essential to confirm the diagnosis.4) Despite a delayed diagnosis appropriate antibiotic therapy can still lead to a good outcome. (+info)
Laceration of the posterior inferior cerebellar artery by suboccipital puncture of the cisterna magna: case report.
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We report the case of a 27 year old man who presented to the emergency room of a hospital with headache, vomiting and an episode of loss of conciousness. A cranial CT scan was normal and the patient discharged. Ten hours later he came to the emergency room of our hospital with the same complaints. A technically difficult cisternal puncture in an anxious patient who moved during the needle introduction was done. The CSF sample showed 1600 intact red blood cells without other alterations. His headache worsened and after 6 hours he became drowsy, numb and exhibited decerebration signs. A new CT scan showed diffuse subarachnoid and intraventricular blood. An emergency angiogram demonstrated laceration of a left posterior-inferior cerebellar artery in its retrobulbar loop with a pseudoaneurysm. He was successfully treated by surgical clipping without injury. Sixteen days later he was discharged with a normal neurological exam. (+info)
Routine lumbar puncture in children with febrile seizures in Ghana: should it continue?
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OBJECTIVES: Performing routine lumbar punctures in children with febrile seizures has been controversial. This study aimed to determine the positive yield of lumbar punctures in a setting where routine lumbar puncture is routinely carried out and to determine if any other parameter could help differentiate bacterial meningitis from the various other diagnoses of children who presented with a febrile seizure. DESIGN: A prospective study was carried out among children aged three months to 15 years of age, hospitalized at the Komfo Anokye Teaching Hospital in Kumasi, Ghana, between July and August 2000. RESULTS: There was a 10.2% (n = 19) positive yield for bacterial meningitis with a case fatality rate of 36.8% (n = 7). Cerebral malaria, which is not easily distinguishable from bacterial meningitis, accounted for 16.1% (n = 30) of the children. Twenty percent of bacterial meningitis patients had a positive blood smear for malaria. The indication for doing a lumbar puncture was similar in both cerebral malaria and bacterial meningitis patients. Signs of meningism were not the primary reason for carrying out a lumbar puncture, even in the group of children who had bacterial meningitis. CONCLUSION: Performing routine lumbar punctures may still have a role to play in the management of children with febrile seizures. (+info)
Case report: greater meningeal inflammation in lumbar than in ventricular region in human bacterial meningitis.
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Differences in the composition of ventricular and lumbar cerebrospinal fluid (CSF) based on single pairs of samples have previously been described. We describe a patient that developed post-surgical recurrent meningitis monitored by daily biochemical and bacteriological CSF analysis, simultaneously withdrawn from lumbar space and ventricles. A 20-year-old Caucasian man was admitted to the ICU after a resection of a chordoma that extended from the sphenoidal sinus to the anterior face of C2. CSF was continuously leaking into the pharyngeal cavity after surgery, and three episodes of recurrent meningitis, all due to Pseudomonas aeruginosa O12, occurred. Our case showed permanent ventricular-to-lumbar CSF gradients of leukocytes, protein and glucose that were increased during the acute phase of meningitis, with the greatest amplitude being observed when bacteria were present in both ventricular and lumbar CSF. This might suggest a greater extent of meningeal inflammation in the lumbar than in the ventricular region. Our case also showed that the increase in intravenous antibiotics (cefepim from 8 to 12 g/day and ciprofloxacine from 1.2 to 2.4 g/day) led to an increase in concentration in plasma but not in CSF. (+info)
Best evidence topic report: reinsertion of the stylet before needle removal in diagnostic lumbar puncture.
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A short cut review was carried out to establish whether re-insertion of the stylet before needle removal changed the incidence of post-lumbar puncture syndrome and headache. Altogether 235 papers were found using the reported search, of which two presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. A clinical bottom line is stated. (+info)
Release of superoxide dismutase into cerebrospinal fluid as a marker of brain lesion in acute cerebral infarction.
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BACKGROUND AND PURPOSE: Evaluation of biochemical patterns in cerebrospinal fluid may add diagnostic and prognostic information. We tested to determine whether the concentration of superoxide dismutase in cerebrospinal fluid is a marker of brain tissue damage in acute ischemic stroke. METHODS: We investigated 36 acute ischemic stroke patients for cerebrospinal fluid activity of the enzyme superoxide dismutase on two occasions shortly after symptom onset (average, day 1 and day 4). RESULTS: In 75% of the patients, the first of two lumbar punctures revealed the maximal superoxide dismutase value. The amount in the cerebrospinal fluid was significantly correlated with the size of infarction on computed tomographic scan (p less than 0.001 by analysis of variance) and to functional impairment and stroke-related mortality during initial hospital stay (p less than 0.002). The correlation of initial superoxide dismutase concentration with the need for long-term institutional care and mortality at 3 months after the stroke was also significant (p less than 0.03). CONCLUSIONS: We conclude that superoxide dismutase in cerebrospinal fluid is a marker of an acute brain lesion and has some value as a prognostic predictor. This small enzyme leaks rapidly from ischemically injured cells. (+info)
Best evidence topic report. Timing of lumbar puncture in suspected subarachnoid haemorrhage.
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A short cut review was carried out to establish how long after onset of headache a lumbar puncture should be carried out to rule out subarachnoid haemorrhage. Altogether 142 papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this best paper are tabulated. A clinical bottom line is stated. (+info)