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Lymphocyte phenotype and subset distribution in normal cerebrospinal fluid.

The distribution of lymphocyte subpopulations in cerebrospinal fluid (CSF) and their phenotypic characteristics were extensively investigated in a group of 18 healthy individuals using two- and three-color flow cytometry. Generally, CD3+ T lymphocytes constituted the vast majority of CSF lymphocytes while the number of B lymphocytes and NK cells were low. Most T lymphocytes exhibited the phenotype of memory/primed cells in both the CD4+ and CD8+ subpopulations. Two markers for recent activation, HLA-DR and interleukin-2 receptor (CD25) were not upregulated when compared with peripheral blood (PB) in the majority of CSF T lymphocytes. However, a fraction of T lymphocytes co-expressing the NK cells markers CD56 and/or CD16 showed a pronounced upregulation of HLA-DR in CSF as compared with PB. This study documents that the cellular composition of the normal CSF differs profoundly from PB regarding all major lymphocyte subpopulations. This has to be taken into account in studies addressing questions regarding cellular immune reactions in the central nervous system under pathological conditions.

Adult↗

Identification of two novel cerebrospinal fluid proteins in non specific mental retardation.

Cerebrospinal fluid (CSF) from twenty three patients with non specific mental retardation and fourteen age matched normal samples was subjected for qualitative analysis of protein profiles by two-dimensional gel electrophoresis (2-DE) and the proteins were visualised by ultra sensitive silver staining. Two proteins designated as mental retardation associated proteins (MRAP-I and MRAP-II) were identified in six male patients out of twenty three patients CSF samples. MRAP-I had an isoelectric point of 7.4 with a relative molecular weight 16.5 kDa, while MRAP-II had an iso-electric point of 7.2 with a relative molecular weight 16.8 kDa. The two proteins are presumed to be originated from brain, as they could not be traced in the serum of patients, nor due to proteolytic degradation. Despite unknown origin and identity, their presence in the CSF of a specific group of mentally retarded male patients suggest their possible clinical utility and to define protein alterations in mental retardation.

Adolescent↗

Computed tomography-guided transsphenoidal closure of postsurgical cerebrospinal fluid fistula: a transmucosal needle technique.

BACKGROUND: Cerebrospinal fluid (CSF) fistula represents a fearful complication of transsphenoidal surgery and, despite careful intraoperative repair and prolonged postoperative lumbar CSF drainage, need for a new surgical intrasphenoidal plasty is not uncommon. METHODS: These cases prompted us to develop a simple, minimally invasive, harmless repeatable technique consisting of a computed tomography (CT)-guided intrasphenoidal injection of fibrin glue through a 12-gauge spinal needle. RESULTS: Five patients presenting with rhinoliquorrhea following a transsphenoidal approach for the excision of pituitary adenomas (three cases) and craniopharyngiomas (two cases) were treated successfully with the presented technique. In two cases the first attempt attained only partial success and therefore the procedure was repeated. In the last two cases, the injection of fibrin glue was preceded by 2 cc of fresh autologous blood, with the aim of enhancing the mechanisms of healing, possibly inducing adhesions and fibrosis. CONCLUSIONS: The proposed method of treatment for CSF leakage following transsphenoidal surgery may represent a valid alternative to the surgical option.

Adult↗

[A case of measles meningoencephalitis with marked increase of plasma cells in cerebrospinal fluid].

Marked increase of plasma cells in cerebrospinal fluid (CSF) was observed in a 22-year-old female patient with measles meningoencephalitis. Typical measles exanthema was followed, 3 days later, by neurological abnormalities such as confusion, severe meningeal signs and bilateral pyramidal signs. Immunological examination showed slight elevation of IgG, normal T cell subsets and NK cell activity in peripheral blood. The antibody titer of measles was 32x in serum (4x after 2 months). CSF contained 167 cells/mm3, 66% of which was plasma cells. Total protein was 75 mg/dl, and IgG (24.5 mg/dl) showed high values. The antibody titer of measles was 4x (1x after 2 months). The antibody index was 7.15 (N = 2). The anti-myelin antibody was 8x. Oligoclonal band in CSF was negative. The appearance of large number of plasma cells in CSF in viral meningoencephalitis is extremely rare in the literature. However, B cell activation in peripheral blood in measles encephalitis has been reported. Therefore, immunologically abnormal findings in CSF of this case suggest marked B cell activation occurring in the central nervous system in measles meningoencephalitis.

Adult↗

Variation of immunoglobulin G and total protein concentrations during lumbar cerebrospinal fluid collection.

In successive lumbar samples of cerebrospinal fluid (CSF), each consisting of 5 ml, immunoglobulin G (IgG) and total protein were determined. Variation was studied by comparing the values in the initial sample with values in succeeding samples. In 13 out of 17 patients, IgG was reduced in sample 2. There was no reduction in the following samples. The concentration of IgG in sample 2 was below 50% of the concentration in sample 1 in 2 patients and below 70% in 9 patients. IgG was also reduced if the concentration in each sample was given as percent of the total protein concentration. The total protein concentration was not significantly reduced during collection of 25 ml of CSF. IgG was increased in sample 2 in 3 out of the 4 patients with neurological diseases since childhood. In 1 patient there was a considerable rise in the total protein concentration after collection of the first 5 ml, without a corresponding rise of IgG concentration. In clinical practice, the portion to which the CSF sample belongs should be noted, and comparison of values from various patients should be made between equivalent samples.

Adolescent↗

Evaluation of spontaneous nasal cerebrospinal fluid leaks.

PURPOSE OF REVIEW: Spontaneous nasal cerebrospinal fluid (CSF) leaks represent a distinct clinical entity that presents important diagnostic and therapeutic challenges. Recognition of the proper demographic group and presenting symptoms, as well as the radiologic features of this disease process, are integral to making the appropriate diagnosis. In addition, this patient group requires special perioperative and intraoperative considerations for suitable management. RECENT FINDINGS: Current literature echoes previously published success rates for endoscopic repair of CSF leaks at or above 90%. Success rates for closure of spontaneous CSF leaks, however, continue to be the lowest in comparison with other CSF leak etiologies. The increased failure rate for spontaneous CSF leak repair is likely due to the increased intracranial pressure present in this patient group. Patients with spontaneous CSF leaks are increasingly being recognized as belonging to a group inclusive of patients with benign intracranial hypertension and empty sella syndrome. SUMMARY: In this review, we highlight the demographic characteristics, clinical presentation and radiologic findings that distinguish spontaneous nasal CSF leak patients from those with other CSF leak etiologies. We also discuss perioperative measures advocated for patients with spontaneous nasal CSF leaks that may aid in the success of their surgical repair.

Cerebrospinal Fluid Rhinorrhea↗

Development and evaluation of 16S rDNA microarray for detecting bacterial pathogens in cerebrospinal fluid.

The rapid identification of bacteria in cerebrospinal fluid (CSF) is very important for patient management and antimicrobial therapies. We developed a 16S DNA microarray-based method that targets 16S rDNA and can directly detect bacteria from CSF without cultivation. Universal primers and specific probes were designed from the 16S rDNA sequence data retrieved directly from the GenBank database. The specificity of the assay is obtained through a combination of microarray hybridization and enzymatic labeling of the constructed specific probes. Cultivation-dependent assays were used as reference methods in the development and evaluation of the method. With the exception of Mycobacterium tuberculosis and Proteus mirabilis, forty-five positive blood culture media were successfully differentiated. When this procedure was applied directly to 100 CSF specimens, 29 specimens from 16 patients were positive by bacterial culture and 3 culture-positive CSF specimens produced no hybridized signals. The remaining 26 specimens were correctly identified, including one with mixed infection. The accuracy, sensitivity, and specificity of the assay can be increased further by designing more oligonucleotides for the microarray. This method is versatile and makes it possible to detect more bacteria in a single assay and discriminate different bacterial genera.

Bacteria↗

High-resolution proton magnetic resonance analysis of human cerebrospinal fluid.

High-resolution proton magnetic resonance spectroscopy was used to analyze human cerebrospinal fluid obtained from patients with several neurological problems. The major metabolites measured included glucose, lactate, glutamine, citrate, inositol, acetate, creatine, creatinine, beta-hydroxybutyrate, alanine, and pyruvate. A drug vehicle, propylene glycol, was also measured. Alterations in the cerebrospinal fluid of these metabolites provided information concerning metabolism of the brain. Magnetic resonance spectroscopy offered a simple and rapid means of assessing these and other exogenous and endogenous compounds in diseases affecting the nervous system.

Adult↗

[Polarographic determination of glucose concentration in cerebrospinal fluid of children (author's transl)].

UNLABELLED: Uing the Beckman gluxose analyzer, glucose concentration was determined polarographically in cerebrospinal fluid of 160 boys and 115 girls (ages 1 month-14 years). On the basis of clinical criterions these children were considered to be "healthy". The total number of examined children was 1668. RESULTS: The distribution of the glucose concentration in cerebrospinal fluid was normal. The following values were obtained for the boys and girls: Boys (ages 1-12 months) = 57,0 +/- 13,7 mg/100 ml, girls (ages 1-12 months) = 57,0 +/- 10,4 mg/100 ml, boys (ages 1-14 years) + 63,0 +/- 12,5 mg/100 ml, girls (ages 1-14 years) = 61,5 +/- 12,2 mg/100 ml. No statistical sex-specific differences were observed, but the age-specific investigation revealed that the group of older boys had a statistical higher concentration of glucose in cerebrospinal fluid as compared to the group of younger boys.

Age Factors↗

Clinical significance of Acinetobacter species isolated from cerebrospinal fluid.

Medical records of 54 patients whose cerebrospinal fluid (CSF) cultures were positive for Acinetobacter were retrospectively reviewed. In 34 (63.0%) patients, the Acinetobacter isolates were clinically insignificant. In the other 20 (37.0%) patients, presence of the organism was regarded as clinically significant and specific antimicrobial therapy was administered. Patients with clinically significant Acinetobacter in CSF more frequently resided in intensive care units (p = 0.011), had intracerebral hemorrhage (p = 0.012) or previous CNS infection (p = 0.003), had prior antibiotic exposure (p = 0.011), and had undergone neurosurgical procedures (p = 0.003). Their CSF was characteristic of neutrophilic pleocytosis, an elevated protein level, and a low CSF-to-serum glucose ratio. Apart from fever, no significant statistical differences existed in individual clinical symptoms and signs between the 2 groups of patients, while a combination of symptoms efficiently differentiated clinically significant and insignificant Acinetobacter. The finding of multiple CSF specimens positive for Acinetobacter was highly suggestive of an active CNS infection (p<0.001). The high ratio of clinically insignificant Acinetobacter CSF isolates highlights the importance of careful judgment when the organism is cultured from CSF. Antimicrobial therapy must be initiated promptly in patients with identified risk factors, while unnecessary treatment should be avoided in those without them.

Acinetobacter↗

Creatine kinase BB and neuron-specific enolase in cerebrospinal fluid in the diagnosis of brain insult.

Cerebrospinal fluid (CSF) markers provide useful information about the extent of brain damage. These biochemical indices may also be used when postmortem histopathological examination does not confirm antemortem brain insult. Seven biochemical parameters--creatine kinase (CK), creatine kinase BB isoenzyme (CK-BB), lactate dehydrogenase (LDH), gamma-glutamyltransferase, aldolase, leucine aminopeptidase (LAP), and neuron-specific enolase (NSE)--were analyzed in CSF from 82 cadavers. Case studies were categorized into one of four diagnostic groups. There were 15 cases of head trauma, 23 of hypoxia (hangings, carbon monoxide, and drug poisonings), 23 sudden cardiac death, and 21 miscellaneous cases. The degree of craniocerebral trauma was graded. In CSF there was a statistically significant correlation between the severity of craniocerebral trauma and levels of CK, CK-BB, aldolase, LDH, and LAP. CSF CK-BB [median U/L (range)] for the groupings of head trauma, hypoxia, sudden cardiac death, and miscellaneous were, respectively, 873 (1-12,100), 26 (2-2,780), 16 (1-42), and 18 (0-2,780). Corresponding CSF CK levels were 9,370 (28-67,842), 101 (18-36,840), 180 (10-29,622), and 264 (17-26,556). There were no statistical significant differences among the NSE concentrations in the four diagnostic groups. The testing of biochemical markers could be a reliable indicator of the degree of brain insult in support of morphological studies.

Adolescent↗

Analysis of different surgical approaches for the treatment of cerebrospinal fluid rhinorrhea.

The current treatment method for cerebrospinal fluid (CSF) rhinorrhea is surgical repair of the fistula. The aim of this study was to analyse different surgical approaches used for the treatment of CSF rhinorrhea regarding several preoperative and postoperative variables to determine the optimal method in these patients. Patients' charts were retrospectively reviewed to get the required data. Twenty-six patients who underwent different types of surgical approach for the treatment of CSF rhinorrhea were included in the study. Patients who had extensive comminuted fractures of the anterior cranial base and additional brain injury besides CSF rhinorrhea, mostly as a result of gunshot injuries, underwent craniotomy (n = 14). Osteoplastic frontal sinusotomy was used in two patients with a dural defect located at the posterior wall of the frontal sinus. Uncomplicated CSF fistulas in ten patients, located at the anterior and posterior ethmoid roof and in the sphenoid sinus, were closed with an endonasal endoscopic approach. Postoperative success rate was higher (97 % for intracranial approach, 100 % for extracranial external and endonasal endoscopic approach) for all techniques. Anosmia was the most frequent permanent complication (n = 5), seen after craniotomy. In conclusion, endonasal endoscopic approach can be preferred for the closure of uncomplicated CSF fistula, located at the anterior or posterior ethmoid roof and in the sphenoid sinus, due to its minimal postoperative morbidity. Uncomplicated CSF fistula, located at the posterior wall of frontal sinuses can be repaired extradurally with osteoplastic frontal sinusotomy. Intracranial approaches should be reserved for more complicated CSF rhinorrhea which results from extensive comminuted fractures of the anterior cranial base and is accompanied with intracranial complications.

Adolescent↗

Significance of empty sella in cerebrospinal fluid leaks.

OBJECTIVE: The role of elevated cerebrospinal fluid (CSF) pressures in the pathophysiology of various CSF leaks is not clear. Empty sella syndrome (ESS) is a radiographic finding that can be associated with elevated CSF pressures and may represent a radiographic indicator of intracranial hypertension. We present our experience with CSF leaks of various causes, the prevalence of ESS in the spontaneous and nonspontaneous categories, and the potential pathophysiology and unique management issues of the spontaneous CSF leak group. METHODS: We conducted a retrospective review of medical records, imaging studies, and surgical treatment of CSF leaks in patients treated by the senior author. RESULTS: Sixteen patients with spontaneous CSF leaks and 12 patients with nonspontaneous CSF leaks were surgically treated from 1996 through 2002. In the spontaneous group, 15 patients had complete imaging of the sella turcica. Ten had completely empty sellae and 5 had partially empty sellae, for a total of 100% (15 of 15). In the nonspontaneous group, 9 patients had complete imaging of the sella. Only 11% (1 of 9) had a partially empty sella and that was a congenital leak. Comparison of proportions between these 2 groups was significant (P = 0.01). The spontaneous group consisted primarily of obese, middle-aged females (13 of 16 patients). CONCLUSION: Empty sella probably represents a sign of elevated intracranial pressure that leads to idiopathic, spontaneous CSF leaks. Spontaneous CSF leaks are strongly associated with the radiographic finding of an empty sella and are more common in obese females, similar to benign intracranial hypertension. This unique population may require more aggressive surgical and medical treatment to prevent recurrent or multiple leaks.

Adult↗

Cerebrospinal fluid values in the term neonate.

BACKGROUND: Cerebrospinal fluid (CSF) values in the noninfected neonate are not well-delineated. Studies analyzing these values are inconsistent in the criteria used to define the noninfected population. The purpose of our study was to examine CSF values in neonates in the first 30 days of life in whom infection was more thoroughly excluded than in previous reports. Stringent inclusion criteria defined the noninfected population, and the recently available polymerase chain reaction (PCR) for enteroviruses was used in addition to cultures to help exclude viral disease. Results were also stratified by age in weeks to evaluate for any variability that occurs in CSF values during the first month of life. METHODS: Neonates were selected from subjects enrolled in two studies on aseptic meningitis. Noninfected infants were identified by the following criteria: (1) atraumatic lumbar puncture (< or = 1000 red blood cells/mm3); (2) no antibiotic therapy before lumbar puncture; (3) sterile blood, CSF and urine bacterial cultures; (4) negative CSF viral culture; and (5) negative CSF PCR for enteroviruses. RESULTS: The mean +/- SD total CSF white blood cell count for 108 noninfected neonates was 7.3 +/- 14/mm3 (95% confidence interval 6.6 to 8.0/mm3) with a median of 4/mm3 and a range of 0 to 130/mm3. There were no significant differences in the mean CSF white blood cell counts among age categories. CONCLUSIONS: The application of stringent inclusion criteria and the use of the PCR yielded a population of infants that better represents the noninfected neonate than earlier reports. These values can be used for reference in evaluating the febrile or ill neonate.

Age Factors↗

The use of radionuclide cisternography in the diagnosis of pleural cerebrospinal fluid fistulae.

Radionuclide cisternography (RNC) is an excellent method of studying cerebrospinal fluid (CSF) dynamics and fistulous communications. Two patients are described in which pleural cerebrospinal fluid fistulae were found by this technique. In addition, marking the area presurgically reduced operating room time in one patient. Such communications are important to locate since they can cause significant loss of CSF as well as provide a pathway for pathogens to enter the central nervous system.

Adolescent↗

[Reinvestigation of CSF outflow resistance value in idiopathic normal pressure hydrocephalus--comparing epidural pressure monitoring with lumbar subarachnoid cerebrospinal fluid pressure monitoring].

PURPOSE: To compare the cerebrospinal fluid (CSF) outflow resistance values (Ro) with epidural pressure (EDP) monitoring and lumbar subarachnoid CSF pressure (L-CSFP) monitoring. SUBJECTS AND METHODS: The subjects were 14 patients with possible iNPH (age: 59-74 years old, ratio of male and female 8:6). All the patients were subjected to an infusion test by a single bolus injection method (1 ml/sec., deltaV: 5 ml, t2: 2 min) as prescribed in the Standard of SINPHONI. EDP was monitored by continuous monitoring and the L-CSFP values By intermittent simple glass tube method (SINPHONI) were measured simultaneously. The Ro (RoEDP, RoL-CSFP) calculated from both methods, (1) the correlation of Ro and (2) the Ro threshold in a shunt effective group (E: nine cases) and a non effective group (NE, five cases) were compared. RESULTS: (1) Although a favorable correlation was found between both Ro measurements (r=0.784), the RoEDP was always higher than the RoL-CSFP. (2) The mean Ro values in the E and NE groups were 36.8 +/- 15.7 mmHg/ml/min, and 10 +/- 2.05 mmHg/ml/min for Ro-EDP, 22.1 +/- 13.95 mmg/ml/min and 6.4 +/- 1.7 mmHg/ml/min for RoL-CSFP, respectively. The approximate thresholds in the E and NE groups were 15 mmHg/ml/min for RoEDP and 10 mmHg/ml/min for RoL-CSFP. CONCLUSION: (1) Although the RoEDP is always higher than the RoL-CSFP, a favorable correlation is found between the RoEDP and RoL-CSFP, (2) The Ro thresholds of the E and NE groups in the infusion test are about 15 mmHg/ml/min for RoEDP and 10 mmHg/ml/min for RoL-CSFP. (3) After this, Ro calculation ought to execute by standard of SINPHONI and the Ro threshold of the E and NE groups is about 10 mmHg/ml/min.

Aged↗

Conservative management of patients with cerebrospinal fluid shunt infections.

OBJECTIVE: In patients with cerebrospinal fluid (CSF) shunt infection, removal of the shunt and antibiotic administration is the current standard of care. In 1986, we developed a protocol for the conservative management of patients with infected but functioning shunts. Treatment was based on the administration of a combination of intraventricular and systemic antibiotics. Intraventricular antibiotics were instilled via a separate access device. The purpose of this report is to describe our experience with this therapeutic intervention. METHODS: An observational study of all patients treated for CSF shunt infection between 1986 and 2003 was undertaken. Cure was defined by sterile CSF after completion of therapy and sterile shunt components at next revision or long-term freedom from recurrent infection (follow-up period, 6-88 mo). RESULTS: In total, 43 of 122 patients with CSF shunt infections were treated conservatively according to our protocol. Overall, 84% of these patients were cured, with a 92% success rate for patients with infections caused by bacteria other than Staphylococcus aureus. This included 30 coagulase-negative staphylococcal infections, of which two were treatment failures. We abandoned conservative treatment of patients with Staphylococcus aureus infections after early experience demonstrated that the success rate (four treatment failures in seven patients) was markedly lower than that for other pathogens. During the treatment and follow-up periods, there were three deaths, two of which were unrelated to shunt infection; treatment failure could not be completely excluded in the remaining patient. There was no toxicity related to intraventricular antibiotic administration. The incidence of shunt blockage among patients who were treated conservatively was not significantly different from that among a large cohort of patients with uninfected shunts. Ten patients received part of their courses of treatment as outpatients. CONCLUSION: The success rate of conservative management of patients with CSF shunt infections caused by coagulase-negative staphylococci is comparable with those in the published literature for patients treated conventionally. This form of management avoids surgical intervention, with its attendant risks, and is safe.

Adolescent↗