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Paradoxical postural headaches in cerebrospinal fluid leaks.

Two patients with cerebrospinal fluid (CSF) leak, one at the level of fourth thoracic spine and another with undetermined level of leak, presented with paradoxical postural headaches in that the headaches were present when in a horizontal position and resolved if the patients were upright. One patient improved spontaneously and the other responded to a targeted epidural blood patch. Paradoxical postural headache is yet another headache type that can be associated with CSF leak and CSF volume depletion. Its mechanism is uncertain, but it could be related to congestion and dilatation of cerebral venous sinuses and large veins.

Female↗

A cerebrospinal fluid leucocidin in pyogenic meningitis.

Cerebrospinal fluid (CSF) samples were tested for their cytotoxicity to polymorphonuclear neutrophil leucocytes (PMN) using a 51Cr release assay. Most samples from patients with pyogenic meningitis damaged PMN while normal CSF samples did not. No difference was found between the cytotoxic activity of CSF from patients with pneumococcal meningitis and from patients with meningococcal meningitis. It is, therefore, unlikely that a CSF leucocidin plays an important part in producing the high mortality of pneumococcal meningitis.

Cytotoxicity, Immunologic↗

Effects of inhibitors on chloride outflux from cerebrospinal fluid.

Movement of chloride from cerebrospinal fluid (CSF) to brain or blood is one of the factors that may be involved in regulation of CSF [Cl-], which is important to CSF acid-base balance. We made quantitative measurements of the unidirectional outflux of radiolabeled chloride (38Cl, half-life 37.3 min) from CSF in anesthetized dogs, using ventriculocisternal perfusion (VCP). The outflux of 38Cl from CSF was determined from the difference between the movements of 38Cl and dextran using a one-compartment model. VCP was performed at a rate of 1.4 ml/min for 14 min, and then slowed to 0.28 ml/min. The 38Cl activity decreased to a steady-state level approximately 12% lower than that of dextran within 40-50 min. Under control conditions for the first run (n = 24), the flux was 0.042 +/- 0.003 (SE) ml/min. The outflux under control conditions (n = 6) tended to increase over three separate determinations in a 6-h period, being 136 +/- 19% of the first run on the second run, and 143 +/- 24% on the third. There were no significant changes in 38Cl outflux compared with control ratios after the inclusion of bumetanide in the VCP fluid (n = 6), which inhibits sodium-coupled Cl- transport, with acetazolamide (n = 6), which inhibits carbonic anhydrase, or with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (n = 6), an inhibitor of carrier-mediated anion exchange. These results suggest that the outward movement of chloride from CSF occurs mostly by passive diffusion and is not by mediated transport.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

Clonal expansion and somatic hypermutation of V(H) genes of B cells from cerebrospinal fluid in multiple sclerosis.

The cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients is characterized by increased concentrations of immunoglobulin (Ig), which on electrophoretic analysis shows restricted heterogeneity (oligoclonal bands). CSF Ig is composed of both serum and intrathecally produced components. To examine the properties of intrathecal antibody-producing B cells, we analyzed Ig heavy-chain variable (V(H)) region genes of B cells recovered from the CSF of 12 MS patients and 15 patients with other neurological diseases (OND). Using a PCR technique, we could detect rearrangements of Ig V(H) genes in all samples. Sequence analysis of complementarity-determining region 3 (CDR3) of rearranged VDJ genes revealed expansion of a dominant clone or clones in 10 of the 12 MS patients. B cell clonal expansion was identified in 3 of 15 OND. The nucleotide sequences of V(H) genes from clonally expanded CSF B cells in MS patients demonstrated the preferential usage of the V(H) IV family. There were numerous somatic mutations, mainly in the CDRs, with a high replacement-to-silent ratio; the mutations were distributed in a way suggesting that these B cells had been positively selected through their antigen receptor. Our results demonstrate that in MS CSF, there is a high frequency of clonally expanded B cells that have properties of postgerminal center memory or antibody-forming lymphocytes.

Adolescent↗

The use of cytokine and C-reactive protein measurements in cerebrospinal fluid during acute infective meningitis.

Cerebrospinal fluid (CSF) concentrations of C-reactive protein (CRP), tumour necrosis factor alpha (TNF), interleukin-6 (IL-6), total protein (TP) and white cell count with differential (WCC) have been measured in 24 patients presenting with acute bacterial or viral meningitis and also in a non-infected, non-inflamed control group (n = 24). In acute viral meningitis, CRP levels were not raised when compared to controls and there was a discordance between high levels of the primary inflammatory mediators (IL-6 and TNF) and the low measured CRP levels. CRP levels were raised in cases of bacterial meningitis. A concentration of 100 ng/mL CRP had a sensitivity of 87% for bacterial meningitis. TNF concentrations in the CSF were significantly raised in cases of acute bacterial meningitis (P < 0.001). Smaller but variable elevations were seen in the patients with acute viral meningitis. One patient, who succumbed to bacterial infection, showed low CSF levels of CRP, TNF and WCC but an elevated IL-6 concentration. Another, presenting with low CSF WCC, had raised concentrations of CRP, TNF and IL-6 which pointed to the correct diagnosis of acute bacterial meningitis. The development of methods yielding rapid analysis for these cytokines together with a sensitive assay for CRP in CSF would be a useful adjunct to conventional investigation.

C-Reactive Protein↗

Oligoclonal bands in Devic's neuromyelitis optica and multiple sclerosis: differences in repeated cerebrospinal fluid examinations.

We studied repeated cerebrospinal fluids of patients with Devic's neuromyelitis optica (NMO) and multiple sclerosis (MS). Variations of oligoclonal bands (OBs) had opposite trends in the two groups. In MS, OBs were detected in 399 of 411 patients (97%) and never disappeared. In NMO, OBs were detected in three of 11 patients (27%) and always disappeared. The hypothesis that NMO and MS follow distinct pathogenetic pathways is supported by our findings, which can be useful for the differentiation of NMO from MS.

Adult↗

Elevated cerebrospinal fluid noradrenaline in tardive dyskinesia.

Cerebrospinal fluid was collected from 28 psychiatric (mostly schizophrenic) inpatients from Bombay, India. These included eight patients with tardive dyskinesia, five with spontaneous dyskinesia and 15 without dyskinesia. The samples were flown to the National Institute of Mental Health, Washington, D.C., where they were analyzed "blind" for concentrations of noradrenaline and several monoamine metabolites. Patients with tardive dyskinesia had significantly higher noradrenaline concentrations in the CSF as compared with the other two groups. Spontaneous dyskinesia group had significantly lower concentrations of homovanillic acid in the CSF. Our results support the hypothesis of noradrenergic hyperactivity, rather than postsynaptic dopamine receptor supersensitivity, in tardive dyskinesia.

3,4-Dihydroxyphenylacetic Acid↗

Cerebrospinal fluid vasopressin--changes in depression.

Cerebrospinal fluid (CSF), thyrotropin releasing hormone (TRH), CSF-vasopressin (AVP), plasma-AVP, CSF-osmolality, plasma-osmolality, CSF-adrenaline (A) and -noradrenaline (NA) were measured in psychiatric patients and controls. Psychiatric patients were classified according to ICD-9 and grouped into endogenous depression, non-endogenous depression, mania and schizophrenia. The depressive groups were classified according to the Newcastle Rating Scale for Depression 1965. Severity of disease was quantified by BRMES, BRMS and BPRS. No difference in CSF-TRH levels was seen among the different diagnostic groups and controls. A positive correlation between CSF-TRH and CSF-A was demonstrated. CSF-AVP concentrations were significantly lowered in both endogenous and non-endogenous depression; no correlation with CSF-A or -NA was seen. Neither did any difference between plasma levels of AVP, plasma-osmolality or CSF-osmolality appear among the groups investigated.

Adolescent↗

A diurnal melatonin rhythm in primate cerebrospinal fluid.

Melatonin was measured in cerebrospinal fluid (CSF) withdrawn continuously from partially restrained rhesys monkeys. There was a daily rhythm in CSF melatonin with peak night values 2- to greater than 15-fold higher than day values. The increase occurred shortly after lights were turned off, and the decrease occurred soon after lights were turned on. There was substantial variation in the magnitude of the rhythm among animals. However, there was little day to day variation in the rhythm of individual animals studied for 3 or 6 consecutive days. Although the concentration of melatonin in CSF was lower than that in plasma, the changes in CSF melatonin concentrations seemed to reflect large daily changes in plasma melatonin concentrations.

Animals↗

Cyclic nucleotides in medulloblastomas: correlative study of tumoral and cerebrospinal fluid levels.

The tumoral and cerebrospinal fluid (CSF) levels of cyclic nucleotides and of the main adrenergic metabolites (homovanillic acid and 5-hydroxyindoleacaetic acid) were investigated in a group of children with posterior fossa medulloblastomas. A longitudinal evaluation of CSF change of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), and adrenergic metabolites before and after surgical removal of the tumor mass is presented. Some preliminary patterns concerning correlative levels in the neoplastic tissue are discussed. The relevant increase of cGMP in medulloblastoma specimens and in CSF samples operation and the rapid decrease in the CSF after surgical removal of the tumor seem to suggest a possible role of cyclic nucleotides in the neoplastic growth of these tumors. (Neurosurgery, 7: 359-362, 1980).

Blood-Brain Barrier↗

Tetanus toxoid reactive T lymphocytes in the cerebrospinal fluid of multiple sclerosis patients.

Cerebrospinal fluid (CSF) lymphocytes of 6 multiple sclerosis (MS) patients were cultured with tetanus toxoid (TT) and irradiated autologous antigen presenting cells (APC) followed by propagation of the responding T-cells in interleukin-2 containing medium. TT-reactive cell lines were recovered from 4 of the 6 CSF samples, even though the patients had not been TT booster immunized in recent years. These findings suggest an active circulation of antigen reactive lymphocytes from the systemic immune compartment(s) into the CSF even without recent activation by booster immunization. Since immune reactions to TT are very unlikely to be pathogenic in MS, these findings also indicate that presence of CSF lymphocytes reactive to a particular antigen does not necessarily imply a causal role.

Antigens↗

Increased risk of neurological relapse in acute lymphoblastic leukemias with high levels of cerebrospinal fluid thymidine kinase at diagnosis.

Cerebrospinal fluid thymidine kinase (CSF-TK) was measured at diagnosis in 62 patients with acute lymphoblastic leukemia (ALL) without initial neurological manifestations, who achieved a complete remission after chemotherapy. During the follow-up period, 10 patients developed central nervous system (CNS) involvement. At the onset of the disease mean CSF-TK levels in these subjects were found to be significantly higher than those observed in patients without subsequent CNS complications. In particular, 7/10 (70%) of these patients who presented CSF-TK levels above the upper limit of normal (1.4 U/microliters) had evidence of a neurological relapse, while 49/52 (94.2%) of subjects with presenting CSF-TK levels of up to 1.4 U/microliters did not develop a neurological leukemic disease (p < 0.00001). The white blood cell count at diagnosis was significantly increased, but not directly correlated to CSF-TK levels, in the group with CNS involvement, while age, serum thymidine kinase levels and lactic dehydrogenase, FAB classification or immunophenotype were not different in patients with or without neurological relapse. In conclusion, increased levels of CSF-TK at presentation correlate with a high risk of subsequent CNS involvement in patients with responsive ALL.

Adolescent↗

Persistent posttraumatic cerebrospinal fluid leakage.

OBJECT: Persistent posttraumatic cerebrospinal fluid (CSF) leakage frequently complicates skull base fractures. Although many CSF leaks will cease without treatment, patients with CSF leaks that persist greater than 24 hours may be at increased risk for meningitis, and many will require surgical intervention. The authors reviewed their 15-year experience with posttraumatic CSF leaks that persisted longer than 24 hours. METHODS: The authors reviewed the medical records of 51 patients treated between 1984 and 1998 with CSF leaks that persisted for 24 hours or longer after traumatic head injury. In 27 patients (55%) spontaneous resolution of CSF leakage occurred at an average of 5 days posttrauma. In 23 patients (45%) surgery was required to resolve the leakage. Eight patients (16%) with occult CSF leaks presented with recurrent meningitis at an average of 6.5 years posttrauma. Forty-three (84%) patients with CSF leaks sustained a skull fracture, most commonly involving the frontal sinus, whereas parenchymal brain injury or extraaxial hematoma was demonstrated in only 18 patients (35%). Delayed CSF leaks, with an average onset of 13 days posttrauma, were observed in eight patients (16%). Among patients with clinically evident CSF leakage, the frequency of meningitis was 10% with antibiotic prophylaxis, and 21% without antibiotic prophylaxis. Thus, prophylactic antibiotic administration halved the risk of meningitis. A variety of surgical approaches was used, and no significant neurological morbidity occurred. Three (13%) of 23 surgically treated patients required additional surgery to treat continued CSF leakage. CONCLUSIONS: A significant proportion of patients with CSF leaks that persist greater than 24 hours will require surgical intervention. Prophylactic antibiotic therapy may be effective in this group of patients. Patients with skull base or frontal sinus fractures should be followed to detect the occurrence of delayed leakage. Surgery-related outcome is excellent.

Adolescent↗

Review of spinal pseudomeningoceles and cerebrospinal fluid fistulas.

Spinal pseudomeningoceles and cerebrospinal fluid (CSF) fistulas are uncommon extradural collections of CSF that may result from inadvertent tears in the dural-arachnoid layer, traumatic injury, or may be congenital in origin. Most pseudomeningoceles are iatrogenic and occur in the posterior lumbar region following surgery. The true incidence of iatrogenic pseudomeningoceles following laminectomy or discectomy is unknown; however, the authors of several published reports suggest that the incidence of lumbar pseudomeningoceles following laminectomy or discectomy is between 0.07% and 2%. Pseudomeningoceles are often asymptomatic, but patients may present with recurrence of low-back pain, radiculopathy, subcutaneous swelling, or with symptoms of intracranial hypotension. Very rarely, they present with delayed myelopathy. Although magnetic resonance imaging is the neurodiagnostic study of choice, computerized tomography myelography and radionuclide myelographic study may be helpful diagnostic tools in some cases. Analysis of suspect fluid for Beta2 transferrin may be a useful adjunctive study. Treatment options include close observation for spontaneous resolution, conservative measures such as bed rest and application of an epidural blood patch, lumbar subarachnoid drainage, and definitive surgical repair.

Diskectomy↗

Spinal pseudomeningoceles and cerebrospinal fluid fistulas.

Spinal pseudomeningoceles and cerebrospinal fluid (CSF) fistulas are rare extradural collections of CSF that result following a breach in the dural-arachnoid layer. They may occur due to an incidental durotomy, during intradural surgery, or from trauma or congenital abnormality. The majority are iatrogenic and occur in the posterior lumbar region following surgery. Although they are often asymptomatic, they may cause low-back pain, headaches, and even nerve root entrapment. Leakage of CSF from the wound may cause a fistulous tract, which is a conduit for infection and should be repaired immediately. Diagnosis can be confirmed on clinical examination or imaging studies including magnetic resonance imaging, computerized tomography myelography, and radionuclide myelography. Treatment must be specific to each patient because the timing, size, symptoms, and location of the dural breach all affect the choice of therapy. Nonsurgical methods may be used, but more frequently operative repair is required. In this article, the authors review the diagnosis and treatment of spinal pseudomeningoceles and CSF fistulas.

Blood Patch, Epidural↗

[Neurotransmission and sudden infant death. Study of cerebrospinal fluid].

The study of 33 cerebrospinal fluids of infants victims of sudden death shows a very significant increase of the metabolites of dopamine and serotonin. These determinations, compared to a control group, indicate a failure, concerning these two neurotransmitters, which could induce a cardiorespiratory seizure. This failure has likely a multifactorial origin.

Heart Arrest↗

[A quantitative analysis of cerebrospinal fluid flow in posttraumatic syringomyelia].

Cerebrospinal fluid (CSF) flow within the spinal canal and syrinx in posttraumatic syringomyelia were studied by cardiac-gated phase images of magnetic resonance imaging in 12 normal volunteers and 8 patients with syringomyelia. The cardiac-gated phase method was simple and useful for detection of CSF flow; 1) phase modulation was in direct proportion to flow velocity, 2) phase modulation was not affected by the T1 or T2 relaxation time. In normal volunteers, CSF flows caudally during systole and cranially during diastole. The maximum caudal CSF flow velocity at C2 level was from 0.45 cm/sec to 1.71 cm/sec, average; 1.27 cm/sec. All of symptomatic posttraumatic syringomyelia patients had the flow in the syrinx.

Adolescent↗

Cerebrospinal fluid lymphocyte transformations in meningitis.

Cerebrospinal fluid lymphocytes from 13 patients with nonsuppurative meningitis were cultured with antigens derived from Mycobacterium tuberculosis, Sporotrichum schenckii, and herpes simplex. When CSF lymphocytes from five patients with infections associated with these organisms were incubated with "correct" antigen there was increased incorporation of thymidine. The levels were higher than those seen when the cells were incubated with different antigens or when CSF lymphocytes from patients with other causes for their meningitis were cultured with these antigens. A compartmentalization of antigen-specific cells was suggested as CSF lymphocytes had greater stimulation than did peripheral blood lymphocytes from the same patient when incubated with the correct antigen. Transformational assays of CSF lymphocytes may provide a valuable diagnostic aid in certain cases of chronic meningitis.

Adolescent↗