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[Metabolites of neurotransmitters in the cerebrospinal fluid in children].

Metabolites of neurotransmitters, homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) were assessed in the cerebrospinal fluid of 149 children of different age from neonatal age to 13 years by the method of high pressure liquid chromatography with electrochemical detection. The mean concentration of the two metabolites in cerebrospinal fluid correlated indirectly with the childrens age--the highest mean concentrations of HVA and 5-HIAA were found in the group of neonates, lower values in infants and the lowest ones in the group of toddlers and older children. In the group of toddlers and older children with severe mental disorders and repeated tonic-clonic or myoclonic seizures a lower mean 5-HIAA was found in the cerebrospinal fluid than in children of equal age, similarly mentally affected but without seizures in the case-history.

Adolescent↗

Endoscopic repair of cerebrospinal fluid leaks to the sinonasal tract: predictors of success.

INTRODUCTION: Cerebrospinal fluid (CSF) leaks may arise as a complication of endoscopic sinus surgery, trauma, or hydrocephalus, or they may occur spontaneously without any identifiable cause. Despite general agreement that CSF leaks should not be left untreated, their initial management, the surgical indications, and the technique of repair are controversial. OBJECTIVE: We undertook this study to ascertain whether a particular surgical technique or material was more successful for repair. Additionally, we tried to identify which specific characteristics of the patient, the CSF fistula, or the adjunctive treatment influenced the result of the repair. STUDY DESIGN: We completed a retrospective review of all patients undergoing endoscopic repair of a CSF leak at our academic hospitals. RESULTS: Forty-eight patients with 53 CSF fistulas were included in the study. Fifty sites were successfully repaired endoscopically on the first attempt. Three persistent leaks were repaired successfully on the second attempt. Location and size of the leak, cause, technique, and choice of material used for the repair did not significantly affect surgical outcome. However, the presence of hydrocephalus had a statistically significant negative influence on surgical outcome. All patients with increased intraventricular pressure required a ventricular shunt in addition to a second endoscopic repair. CONCLUSION: If the surgical technique is sound, endoscopic repair of CSF leaks is highly successful, independent of the choice of the material and technique used in the repair.

Adolescent↗

Cerebrospinal fluid biogenic amines and biopterin in Rett syndrome.

We evaluated cerebrospinal fluid biogenic amine metabolites in 32 patients with Rett syndrome. Significant reductions were noted in the metabolites of norepinephrine, dopamine, and serotonin, as compared with controls of similar age (p less than 0.001, p less than 0.001, and p less than 0.05, respectively). Tetrahydrobiopterin is an essential cofactor and may be rate-limiting for the synthesis of catecholamines and serotonin. Accordingly, total cerebrospinal fluid biopterin was measured and found to be elevated in patients compared with controls (p less than 0.002). These findings constitute the only biochemical changes detected in Rett syndromes so far.

Adolescent↗

Transnasal endoscopic repair of cerebrospinal fluid fistulas and encephaloceles: surgical indications and complications.

INTRODUCTION: Transnasal endoscopic repair of cerebrospinal fluid (CSF) fistulas is recommended for patients with CSF leaks who do not respond to conservative treatment. It is a safer and more successful alternative to transcranial surgery. PATIENTS AND METHODS: We present our experience on using transnasal endoscopy for the repair of anterior skull base cerebrospinal fluid fistulas. Between 1999 and 2003 we observed 20 patients with CSF rhinorrhea. The etiology was heterogeneous: post-traumatic in 6 cases, iatrogenic in 6 cases (one interesting case of meningioma of the sphenoethmoid plate), dysembryogenetic - due to encephaloceles - in 4 patients (one with Cruzon syndrome and one with Down syndrome) and idiopathic in the other 4 patients. Use of a rigid transnasal endoscope allowed the localization and repair of all fistulas, with the use of fluorescein in 6 cases. Different grafts were used, in particular fat, bone or chondral septum with mucoperiosteum or perichondral mucosa. Generally the graft was inserted with the underlay or the sandwich technique. Lumbar drainage was used in the postoperative period only in 6 cases. No antibiotic prophylactic therapy was used. RESULTS: Endoscopy was successful in 90 % of patients at the first attempt, and in 95 % of patients at the second approach. We had two late complications such as infections. In one child with a post-traumatic fistula and shunt for hydrocephalus, we observed meningitis 2 years after the first endoscopic surgery and he underwent both transnasal endoscopic surgery and transcranial surgery. The second patient was a woman with a spontaneous fistula, who had rhinoliquorrhea three years after the first surgical treatment. During surgery a strange similar purulent material filling the submucous space of the ethmoid roof was found, suggestive for an intranasal abscess that was removed. We did not see any complications such as hematomas or seizures. The follow-up (range: 6 months to 3 years) made both with MRI and rhinoscopy has not shown any relapse until now in 19 of 20 patients treated only with endoscopy. CONCLUSIONS: The endoscopic approach is highly effective and safe in the treatment of CSF fistulas, with great visualization and minimal invasiveness, for which it is associated to a very low morbidity. The fluorescein technique is extremely helpful for the diagnosis and surgery of CSF leaks.

Adolescent↗

[Diagnostic significance of cerebrospinal fluid IgG determination by radial immunodiffusion].

The concentration of immunoglobulin G in 455 cerebrospinal fluids has been determined. The results obtained are discussed together with the corresponding total protein and gamma-globulin values. Classification by seven constellations and their assignment to four groups of diseases (acute and inflammatory diseases, chronically inflammatory diseases, E. d., and tumors) allows valuable information to be obtained about the diagnostic significance of IgG determination in the cerebrospinal fluid. This is true especially of E. d. and also applies to an assessment of the activity of inflammatory processes. It is evident from the results of these studies that an evaluation of the IgG value is not possible without considering the total content of protein. The value found for the quotient (see article).

Central Nervous System Diseases↗

[Fronto-basal cerebrospinal fluid fistula. Diagnosis and its significance in the etiology of mixed purulent meningitis].

By means of own clinical observations and reports from the literature we want to emphasize the clinical importance of early diagnosis of abnormal communications between the subarachnoid space and other body compartments. Clinical symptoms of these conditions are rather sparse; the diagnosis has to be made therefore by a high index of suspicion. The most relevant criteria for further investigation of a cerebrospinal fluid fistula are in summary: Recurrent purulent meningitis. Sometimes a considerable time interval between the first episode of purulent meningitis and further disease states can be observed. History of trauma to the bony structure encasing the central nervous system and liquorrhea at least sometimes in the past. The trauma may have occurred sometimes in early childhood or infancy and thought to be trivial. A positive culture of pneumococci in the cerebrospinal fluid is the least characteristic sign. Some patients are partially treated with antibiotics before the diagnosis is made and this might prove sufficient, not to culture organisms in the cerebrospinal fluid. In case of a recurrent meningitis a further investigation has to be done to arrive at a satisfactory explanation. A cerebrospinal fluid fistula has to be excluded by all means. If a fistula is found, further recurrences can be prevented only if the abnormal communication is closed surgically.

Brain Diseases↗

[Apolipoproteins AI, B100, CII, CIII and E in human cerebrospinal fluid].

Apolipoproteins AI, B100, CII, CIII and E contents were measured by radial immunodiffusion assay kits developed by our Research Unit. The apolipoprotein in 10 human cerebrospinal fluid samples was determined. Results show that there are no apo B100, CII or trace apo CIII in human cerebrospinal fluid, the levels of apo AI in cerebrospinal fluid are 1.00 +/- 0.54 mg/dl with a range of 0.35-2.00 mg/dl and the apo E content is 0.69 +/- 0.16 mg/dl with a range of 0.51-0.99 mg/dl. The results are discussed.

Apolipoprotein A-I↗

[Diagnostic value of cerebrospinal fluid study in multiple sclerosis].

Multiple sclerosis ist a very frequent chronic inflammatory disease of the central nervous system. Since clinical and neuro-imaging findings often may be ambiguous, cerebrospinal fluid examination has received great importance for diagnosis. By that method it becomes possible to differentiate inflammatory from noninflammatory diseases. Furthermore, cerebrospinal fluid findings are discussed which seem to be characteristic for multiple sclerosis.

Antibodies, Viral↗

Role of cerebrospinal fluid diversion in posterior fossa tumor surgery.

OBJECTIVE: To assess the role of cerebrospinal fluid diversion in posterior fossa tumor surgery. DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: This study was conducted at the Department of Neurosurgery, Pakistan Institute of Medical Sciences (PIMS), Islamabad from February 2000 to July 2002 over a period of two and-a-half years. SUBJECTS AND METHODS: Clinical, radiological and operative records of the patients who were operated for posterior fossa tumors were studied. Absolute and relative frequencies of the patients who were managed with external ventricular drainage (EVD) or ventriculoperitoneal shunt (VPS) were determined. Mean age and male to female ratio were also noted. RESULTS: There were 48 patients who were operated for posterior fossa tumors. Mean age was 23 years. Male to female ratio was 1.2:1. VPS was done in 14 patients (29%) pre-operatively, in one patient (2%) per-operatively and in 2 patients (4%) postoperatively. EVD was done in 33 patients out of whom 2 patients were shunted post-operatively. Sixty-five percent of the patients remained shunt-free. CONCLUSION: Although management of hydrocephalus secondary to posterior fossa tumors is controversial, majority of the patients need temporary cerebrospinal fluid diversion

Adult↗

Sequestration of virus-specific T cells in the cerebrospinal fluid of a patient with varicella zoster viral meningoencephalitis.

The frequency of virus-specific T cells in the cerebrospinal fluid of a patient with viral infection of the brain and meninges was determined by using a single-T-cell cloning technique where a representative sampling of T cells was cloned from the cerebrospinal fluid of a patient with varicella zoster viral (VZV) meningoencephalitis. That the derived T-cell clones were in fact clonal was shown by demonstrating, on Southern blot analyses, unique rearrangements of the T-cell antigen-receptor beta-chain genes of each clone. Five out of the 15 of the T4+ (CD4), 0/4 of the T8+ (CD8), and 0/1 of the T4+T8+ T-cell clones proliferated to VZV, while no clones proliferated to mumps virus or myelin basic protein. There was no clonal expansion of any VZV-reactive T cell in this patient's cerebrospinal fluid. As VZV meningoencephalitis is thought to be due to the reactivation of a dormant herpes zoster viral infection, it can be regarded as a secondary immune response. The presence of different T-cell receptor beta-chain gene rearrangements in each T-cell clone suggests that the T-cell response was polyclonal. These results demonstrate that a high frequency of polyclonal, T4+ antigen-specific T cells can be found in a naturally occurring, localized, immune response.

Antigens, Differentiation, T-Lymphocyte↗

Chronic intracranial hypertension with unexplained cerebrospinal fluid pleocytosis.

In a retrospective review of all cases with a diagnosis of idiopathic intracranial hypertension in two academic departments of neurology over a nine-year period, the authors identified six patients with a clinical course typical of idiopathic intracranial hypertension (IIH) except for the finding of cerebrospinal fluid pleocytosis. There were five women and one man with a mean age at presentation of 25.7 years (range, 25-32 yr). All were obese but had no other associated medical conditions or identifiable risk factors for IIH. In five patients, all or most cerebrospinal fluid cells were lymphocytes. Cerebrospinal fluid pleocytosis persisted for several months in all patients. Patients underwent a thorough laboratory and neuroimaging evaluation that did not reveal a primary cause. Medical treatment directed solely at lowering intracranial pressure was effective in five patients; one patient required lumboperitoneal shunting. Ophthalmic manifestations of increased intracranial pressure stabilized or remitted after treatment was withdrawn with a mean follow-up period of 33 months (range, 14-55 mo). Some patients may present with idiopathic chronic meningitis and elevated intracranial pressure that responds to treatment used for IIH.

Acetazolamide↗

[Migraine and histamine: determining histidine in plasma and cerebrospinal fluid during migraine attacks].

We studied the plasma levels and cerebrospinal fluid (CSF) levels in twenty-nine patients suffering from migraine without aura and in eighteen others with aura. The samples were obtained during migraine attacks. We compared the results obtained with those from twenty-seven control subjects. Histidine levels in plasma were 1.18 +/- 0.51 mg/dl for the control group, 1.75 +/- 0.39 mg/dl in those suffering from migraine without aura and 2.07 +/- 0.64 mg/dl in those cases of migraine with aura. In both plasma and in cerebrospinal fluid concentrations of histidine were greater in patients with migraine than in controls (p < 0.001). Histidine is an amino acid precursor of histamine and its abnormalities may be demonstrative of the participation of this amine in migraine attacks, possibly within the state of neuronal hyperexcitability.

Adolescent↗

Fast inversion-recovery MR: the effect of hybrid RARE readout on the null points of fat and cerebrospinal fluid.

PURPOSE: To evaluate the effect of the hybrid RARE (rapid acquisition with relaxation enhancement) readout, commonly coupled to inversion-recovery pulse sequences, on the null inversiton time (TI) of fluid and fat using both phantoms and human volunteers. METHODS: Two phantoms, simulating fat (phantom A) and cerebrospinal fluid (phantom B), respectively, were imaged using a fast inversion-recovery sequence that coupled an inversion-recovery preparation pulse to a hybrid RARE readout. At repetition times (TRs) ranging from 700 to 20,000, the TI necessary to null the signal from each phantom (null TI) was determined for an echo train length of 4, 6, 8, 10, 12, 14, 16, 18, and 20, respectively. Plots of null TI versus echo train length at different TRs were generated for both phantoms. Fast inversion-recovery MR imaging of the cervical spine and brain was performed in healthy volunteers. At a fixed TR and TI, the adequacy of signal suppression from bone marrow and cerebrospinal fluid was assessed as a function of echo train length. RESULTS: There was a gradual decrease of null TI for both phantoms with echo train length. This decrease persisted at longer TRs for phantom B (T1 = 3175 +/- 70 milliseconds) than for phantom A (T1 = 218 +/- 5 milliseconds). In the human volunteers, there was a gradual loss of suppression of signal from bone marrow and cerebrospinal fluid, with changes in the hybrid RARE readout. CONCLUSION: To optimize specific tissue suppression, radiologists implementing fast inversion-recovery MR imaging should be aware of the effects of the hybrid RARE readout on null TI.

Adipose Tissue↗

Levodopa and 3-O-methyldopa in cerebrospinal fluid after levodopa-carbidopa association.

Since motor fluctuations in Parkinsonian patients might be, at least in part, explained by an antagonism between levodopa (LD) and its metabolite 3-O-methyldopa (3-OMD) at blood-brain-barrier (BBB), we decided to study LD and 3-OMD plasma and cerebrospinal fluid (CSF) levels in subjects undergoing lumbar puncture for diagnostic purposes. After informed consent, 70 subjects took a tablet of carbidopa-levodopa association (Sinemet or Sinemet-CR) 0.5, 1, 2, 4, 8, 12 h before blood and lumbar cerebrospinal fluid collection. LD and 3-OMD were determined by an HPLC-electrochemical method. The subjects treated with Sinemet-CR had lower LD cerebrospinal fluid concentrations along with lower LD and higher 3-OMD plasma concentrations. This pattern of LD cerebrospinal fluid concentrations may be explained by means of a transport competition between LD and 3-OMD at blood brain barrier level.

Adolescent↗

Cerebrospinal fluid glycine in nonketotic hyperglycinemic: effect of treatment with sodium benzoate and a ventricular shunt.

In three infants with nonketotic hyperglycinemia, glycine was increased three-to fourfold in plasma, 13- to 28-fold in lumbar spinal fluid, and was higher yet in ventricular fluid. Oral sodium benzoate lowered cerebrospinal fluid (CSF) glycine by greater than 40%, but did not change the abnormal plasma: CSF ratio. An adult control, made hyperglycinemic with oral glycine, had a normal plasma: CSF ratio. Treatment of one patient with sodium benzoate from birth did not prevent mental retardation; the degree of brain stem depression was a function of CSF glycine in another patient. The persistance of glycine elevation in CSF, although therapy maintained normal concentration in plasma, appears to be caused by overproduction in brain and limitation of the high-capacity lumbar spinal reabsorptive mechanism. Treatment through lowering of CNS glycine by use of a ventricular shunt was explored.

Amino Acid Metabolism, Inborn Errors↗

A Chronic Fatigue Syndrome - related proteome in human cerebrospinal fluid.

BACKGROUND: Chronic Fatigue Syndrome (CFS), Persian Gulf War Illness (PGI), and fibromyalgia are overlapping symptom complexes without objective markers or known pathophysiology. Neurological dysfunction is common. We assessed cerebrospinal fluid to find proteins that were differentially expressed in this CFS-spectrum of illnesses compared to control subjects. METHODS: Cerebrospinal fluid specimens from 10 CFS, 10 PGI, and 10 control subjects (50 mul/subject) were pooled into one sample per group (cohort 1). Cohort 2 of 12 control and 9 CFS subjects had their fluids (200 mul/subject) assessed individually. After trypsin digestion, peptides were analyzed by capillary chromatography, quadrupole-time-of-flight mass spectrometry, peptide sequencing, bioinformatic protein identification, and statistical analysis. RESULTS: Pooled CFS and PGI samples shared 20 proteins that were not detectable in the pooled control sample (cohort 1 CFS-related proteome). Multilogistic regression analysis (GLM) of cohort 2 detected 10 proteins that were shared by CFS individuals and the cohort 1 CFS-related proteome, but were not detected in control samples. Detection of >or=1 of a select set of 5 CFS-related proteins predicted CFS status with 80% concordance (logistic model). The proteins were alpha-1-macroglobulin, amyloid precursor-like protein 1, keratin 16, orosomucoid 2 and pigment epithelium-derived factor. Overall, 62 of 115 proteins were newly described. CONCLUSION: This pilot study detected an identical set of central nervous system, innate immune and amyloidogenic proteins in cerebrospinal fluids from two independent cohorts of subjects with overlapping CFS, PGI and fibromyalgia. Although syndrome names and definitions were different, the proteome and presumed pathological mechanism(s) may be shared.

Adolescent↗

Immunoglobulin D in cerebrospinal fluid.

Immunoglobulin D (IgD) was measured by radioimmunoassay in paired cerebrospinal fluid and serum samples from patients with various neurological diseases. The IgD index was calculated for every patient and compared with the IgG index. An increased IgD index was found in 18 out of 41 patients suffering from multiple sclerosis and in 52 out of all 122 patients investigated. An increased IgD index did not always coincide with an increased IgG index. An increased IgD index suggests an abnormal intrathecal synthesis of this immunoglobulin within the central nervous system. We conclude that the determination of IgD in the cerebrospinal fluid yields additional information on immunological reactions within the central nervous system.

Humans↗

Cerebrospinal fluid findings in patients with symptoms suggesting chronic Lyme borreliosis.

BACKGROUND: Patients with non-specific long-lasting symptoms such as headache, concentration disturbances, and vertigo and who have positive serum borrelial antibody titres are often assumed to have chronic Lyme borreliosis. Because of the possibility that they may have central nervous system involvement they are frequently treated with courses of i.v. ceftriaxone. We assessed central nervous system involvement by examining cerebrospinal fluid samples in a group of such patients. PATIENTS AND METHODS: Adult patients who qualified for the study had non-specific symptoms suggesting central nervous system involvement for longer than six months (but without overt clinical signs of such involvement) and positive serum borrelial antibody titres and/or erythema migrans prior to the onset of symptoms. Cerebrospinal fluid was examined in all patients. RESULTS: None of the 77 patients included in the study (median duration of symptoms 18 months) had pleocytosis and there was no isolation of Borrelia burgdorferi sensu lato from cerebrospinal fluid. Mildly elevated protein concentration and intrathecal borrelial IgG antibody synthesis were demonstrated in 16 (21%) and 7 (9.1%) patients, respectively. CONCLUSIONS: In patients with non-specific long-lasting symptoms attributed to Lyme borreliosis but with the absence of overt clinical signs suggesting central nervous system involvement, the findings of cerebrospinal fluid examination are usually in the normal range. Routine treatment of such patients with i.v. ceftriaxone is not to be encouraged.

Adult↗