[Phase contrast magnetic resonance imaging of cerebrospinal fluid flow through the aqueduct of sylvius in chronic tension-type headache].

OBJECTIVE: To study the cerebrospinal fluid (CSF) flow through the aqueduct of sylvius in chronic tension-type headache patients with phase contrast magnetic resonance imaging. METHODS: Phase contrast magnetic resonance imaging (MRI) of the CSF flow through the aqueduct was obtained from 17 patients with chronic tension-type headache and 26 control subjects. A software for CSF flow was applied for MRI data analysis both qualitatively and quantitatively. RESULTS: The CSF through the aqueduct flew in the caudal and cranial directions with the rhythm of the heartbeat in both groups. There were 2 types of flow curves: the smooth "U" and the wave, which were 25 vs 1 in the controls and 11 vs 6 in the patients (P<0.05), respectively. The mean caudocranial flow rate through the aqueduct was (0.235±0.157) mL/s vs (0.133±0.106) mL/s (P<0.05) and the velocity was (6.023±2.654) cm/s vs (3.479±2.364) cm/s (P<0.05), and the mean craniocaudal flow rate was (-0.358±0.201) mL/s vs (-0.190±0.141) mL/s (P<0.05) and the velocity was (-8.263±3.020) cm/s vs (-4.788±2.862) cm/s (P<0.05), respectively. CONCLUSION: The CSF flow curve, rate and velocity through the aqueduct in the patients with chronic tension-type headache is anomalous in comparison with the controls.

Cerebrospinal fluid from patients with multiple system atrophy promotes in vitro α-synuclein fibril formation.

The aggregation of α-synuclein (αS) in the central nervous system (CNS) is the hallmark of multiple system atrophy (MSA) and Lewy body diseases including Parkinson's disease (PD) and dementia with Lewy bodies (DLB) (α-synucleinopathies). To test the hypothesis that patients with α-synucleinopathies have a CNS environment favorable for αS aggregation, we examined the influence of cerebrospinal fluid (CSF) from patients with MSA (n=20), DLB (n=8), and PD (n=10) on in vitro αS fibril (fαS) formation at pH 7.5 and 37°C using fluorescence spectroscopy with thioflavin S, compared with those with hereditary spinocerebellar ataxia (hSCA) (n=16), and tension-type headache (n=7). CSF from MSA patients (MSA-CSF) promoted fαS formation more strongly than PD-, hSCA-, or headache-CSF. By electron microscopic analyses, the width of fαS formed in MSA-CSF was significantly greater than others. MSA may have a CSF environment particularly favorable for fαS formation.

Clinical study on CXCL13, CCL17, CCL20 and IL-17 as immune cell migration navigators in relapsing-remitting multiple sclerosis patients.

BACKGROUND: There has been a growing evidence for the role of chemokines in the pathology of multiple sclerosis. Recently, there has been great emphasis placed on humoral immunity and the T(H)-17 response, which has not yet been thoroughly described in MS. The aim of this study was to investigate the role of specific chemokines involved in B-cell migration (CXCL13) and in the T(H)-17 immune response (IL-17, CCL17, CCL20). METHODS: Using ELISA, the chosen chemokine concentrations were measured in the serum and cerebrospinal fluid of relapsing-remitting MS patients with both active and stable disease, and the relapse prediction rate was calculated. RESULTS: We found that the CSF concentrations of CXCL13 in patients with RRMS both, during relapse and remission, were significantly higher than in controls. CCL17 and CCL20 were not detected in CSF in either of the groups, whereas serum CCL20 level was significantly higher in remission than during relapse. Intravenous methylprednisolone treatment of patients with relapse did not influence serum CXCL13 and CCL20 levels. However, it did lower CCL17 and IL-17 concentrations. CONCLUSIONS: CXCL13 is an important mediator in MS that is strongly linked to the neuroinflammatory activity of the disease. However, more studies are needed for elucidating the roles of CCL17, CCL20 and IL-17 in MS pathology.

Rostrocaudal dynamics of CSF biomarkers.

The rostrocaudal gradient (RCG) of markers present in cerebrospinal fluid (CSF) has not been studied adequately due to lack of appropriate control populations and ethical restrictions. The aim of this study is to understand the rostrocaudal gradient of CSF biomarkers. We contacted a study comparing CSF levels of seven biomarkers from cisternal (rostral) and lumbar (caudal) CSF obtained from patients with trigeminal neuralgia and tension-type headache. The RCGs of CSF/serum albumin ratio, 8-isoprostane. GFAP, total tau and beta amyloid protein were higher than one. The RCGs of lactate, VEGF and the heavy chain of neurofilament protein were lower than one. The study provides new values for several commonly examined markers of cisternal CSF. Knowledge of the RCG gradient of different CSF markers is important in interpreting studies reporting ventricular CSF values.

Cerebrospinal fluid cytokine levels in migraine, tension-type headache and cervicogenic headache.

Cytokines have been measured in cerebrospinal fluid (CSF) from headache patients [infrequent episodic tension-type headache (TTH) and migraine with or without aura, all during attack, and cervicogenic headache] and compared with levels in pain-free individuals. Both proinflammatory [interleukin (IL)-1beta, tumour necrosis factor-alpha and monocyte chemoattractant protein-1 (MCP-1)] and anti-inflammatory cytokines [IL-1 receptor antagonist (IL-1ra), IL-4, IL-10 and transforming growth factor-beta1 (TGF-beta1)] were included. There were significant group differences in IL-1ra, TGF-beta1 and MCP-1 in episodic TTH and migraine compared with controls, and a significant difference in MCP-1 between cervicogenic headache and migraine with aura. Intrathecal MCP-1 correlated with IL-1ra, IL-10 and TGF-beta1 in episodic TTH, and MCP-1 with IL-10 in migraine with aura. Cytokine increases were modest compared with those often accompanying serious neurological conditions, and may represent a mild response to pain. We believe this to be the first comparative study of CSF cytokine levels in connection with headache.

Erythropoietin in cerebrospinal fluid: age-related reference values and relevance in neurological disease.

We aimed to establish age-related reference values for Erythropoietin (EPO) in cerebrospinal fluid (CSF) and to evaluate concentrations in neurological diseases. CSF and serum EPO was measured in controls with tension-type headache (CTTH), in patients with ALS, dementia and depression using ELISA technique. Stability experiments showed CSF EPO to be stable for two and a half months and over two thaw/freeze cycles. A positive correlation of CSF EPO with age was found (P<0.01). We found a CSF/serum EPO concentration ratio of 0.126, pointing towards an intrathecal synthesis of EPO. The ALS group showed significantly lowered CSF EPO compared to age-matched CTTH (P<0.012), whereas the dementia and depression group showed no significant differences compared to CTTH.The establishment of age-related reference values in a large cohort of controls will improve the interpretation of future CSF EPO evaluations in neurological diseases.

Relationship between chronic tension-type headache, cranial hemodynamics, and cerebrospinal pressure: study involving provocation with sumatriptan.

OBJECTIVE: To study the relationship between chronic tension-type headache, cranial hemodynamics, and cerebrospinal pressure. BACKGROUND: Cerebrospinal pressure has been found to be above 200 mm in about 50% of patients with chronic tension-type headache. METHODS: Heart rate, blood pressure, common carotid artery diameter and blood flow, and craniovascular resistance and pain at regular intervals before, during, and after head-down tilt-a procedure which increases cerebrospinal pressure, were recorded. After head-down tilt, subcutaneous injections of either placebo or 6 mg of sumatriptan were administered. Chronic tension-type headache intensity before and after withdrawal of 20 mL of cerebrospinal fluid was documented. Cerebrospinal pressure and chronic tension-type headache intensity were measured after subcutaneous injection of 6 mg of sumatriptan. RESULTS: Head-down tilt provoked an increase of headache compared with baseline. Common carotid artery blood flow decreased and craniovascular resistance increased after sumatriptan injection, but not after placebo injection. The pain decreased after head-down tilt and placebo injection, but not after sumatriptan injection. Chronic tension-type headache intensity decreased in all 4 patients studied after withdrawal of 20 mL of cerebrospinal fluid. Cerebrospinal pressure increased in 5 patients with chronic tension-type headache after subcutaneous injection of 6 mg of sumatriptan with slight or no increase of pain. CONCLUSION: The results indicated that cerebrospinal pressure or intracranial venous pressure (or both) are related to chronic tension-type headache.

Nitric oxide metabolite determinations reveal continuous inflammation in multiple sclerosis.

Nitric oxide (NO) is formed as a consequence of induction of the iNOS enzyme during inflammatory disorders. To investigate NO production in multiple sclerosis (MS), we determined the concentrations of its oxidation products (NOx) in the cerebrospinal fluid (CSF) and plasma of 61 MS patients. The patients were divided into three groups on the basis of their clinical disease activity. The total levels of NOx in CSF were significantly increased in all MS groups as compared to healthy controls and tension headache patients. CSF nitrite correlated with clinical disease activity. At exacerbation, the CSF nitrite levels exceed the plasma level. This suggests that clinical disease activity is due to a CNS inflammatory response, which is more intense and qualitatively different from that during clinical stable phases. This study supports NO involvement in the pathogenesis of MS and determination of nitrite levels may be useful a surrogate marker for disease activity.

[Tumor necrosis factor alpha (TNF-alpha) in patients with ischemic stroke]. / Czynnik martwicy nowotworu alfa (TNF-alfa) u chorych z udarem niedokrwiennym mózgu.

Tumour necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine. Stroke induces a rapid increase in TNF-alpha levels within and around the focus of damaged brain. The aim of our study was to evaluate, whether patients with stroke differ from control patients in the concentrations of TNF-alpha in cerebrospinal fluid and serum. We studied TNF-alpha levels in cerebrospinal fluid and serum in 30 patients with stroke within 24 h after onset of neurological signs and in 15 patients of control group with the diagnosis of tension headache and neurasthenia. In patients with stroke the levels of TNF-alpha in the cerebrospinal fluid and serum were significantly higher in comparison with control group. The results of our study may suggest the overproduction of TNF-alpha during first twenty-four hours of stroke.

The impact of HIV infection on primary headache. Unexpected findings from retrospective, cross-sectional, and prospective analyses.

Headache is one of the most important factors influencing the quality of life in patients infected with the human immunodeficiency virus type 1 (HIV). However, only symptomatic headache but not changes or primary headache types during HIV infection have been studied to date. Therefore, we aimed to determine the impact of an HIV infection on frequency and semiology of different primary headache types. Patients with confirmed HIV type 1 infection underwent a neurological examination, neuroimaging or EEG, and a standardized interview. Time pattern and symptoms of headaches (cross-sectional analysis), changes of headaches preexisting to their infection (longitudinal retrospective analysis), and changes of primary headaches during a 2-year follow-up (longitudinal prospective analysis) were evaluated as were the correlations between these headache patterns and different markers of HIV infection. One hundred thirty-one consecutive HIV-infected patients without evidence of a cerebral manifestation except mild encephalopathy were enrolled. The point prevalence of migraine was 16.0% (confidence interval (CI) 10.1-25.4%), of headache with a semiology of tension-type headache 45.8% (CI 33.7-62.2%), and of other headache types 6.1% (CI 3.0-12.5%). During the natural course of infection, the migraine frequency significantly decreased in the retrospective and in the prospective analyses, whereas the frequency of the headache with a semiology of tension-type headache significantly increased in all three analyses. In 20% of all patients, the tension-type headache could be considered as symptomatic due to the infection but not due to focal or general cerebral lesions. Changes of primary headache were significantly associated with different stages of the infection and with the presence of mild encephalopathy but not with antiretroviral treatment or CD4 cell count. HIV infection seems to be associated with a progressive decrease in migraine frequency and intensity which probably is related to the immunological state of the patients. Tension-type headache becomes more frequent during HIV infection. However, this can in part be related to secondary headache caused by the HIV in less than 50% of patients with tension-type headache. The progressing immunological deficiency of HIV-infected patients seems to influence pain processing of primary headache types in different ways.

Increased cerebrospinal fluid Met-enkephalin immunoreactivity in patients with chronic tension-type headache.

Cerebrospinal fluid (CSF) concentration of Met-enkephalin immunoreactivity (Met-enkephalin-ir) was determined by radioimmunoassay in 47 patients with chronic tension-type headache and in 47 headache-free control subjects. Thirty-nine of the controls were patients receiving spinal analgesia before surgery for diseases not associated with pain; 8 were healthy paid volunteers. Patients reporting migraine more than 1 day per month were excluded. Pericranial tenderness, nociceptive flexion reflex and thermal pain thresholds were determined in the majority of the patients. The median level of CSF Met-enkephalin-ir was significantly higher (115 pmol/l) (quartiles (107-134) pmol/l) in the headache patients than in the controls (median 79 pmol/l) (quartiles (73-87) pmol/l) (Mann-Whitney, P < 0.001). No indication of sex-difference or correlation with age with respect to CSF Met-enkephalin-ir was found. No correlation was found between CSF Met-enkephalin-ir and either pericranial tenderness, nociceptive flexion-reflex threshold, or thermal pain threshold. There was no indication of correlation between consumption of mild analgesics and CSF Met-enkephalin-ir. The higher levels of CSF Met-enkephalin-ir in the headache patients may be indicate activation of the enkephalinergic antinociceptive system at the spinal/trigeminal level, whereas the beta-endorphinergic system appears normal. This enkephalinergic activation may be caused by increased activity in the primary nociceptive afferents, or may be compensatory to decreased activity in other endogenous antinociceptive systems than the opioid.

Effect of sulpiride or paroxetine on cerebrospinal fluid neuropeptide concentrations in patients with chronic tension-type headache.

In lumbar cerebrospinal fluid (CSF) obtained from patients with chronic tension-type headache (CTH), the concentrations of beta-endorphin, met-enkephalin, dynorphin, cholecystokinin (CCK), calcitonin gene-related peptide (CGRP), and somatostatin were measured before and after 8 weeks of treatment with sulpiride or paroxetine. We previously reported higher than normal met-enkephalin concentrations in CTH. The present study reveals normal basal concentrations of CCK, CGRP and somatostatin and slightly decreased dynorphin in the same patients. Treatment with sulpiride or paroxetine did not change the concentration of any of the neuropeptides measured. These data suggest central changes in opioid systems but not in other peptide systems (CCK, CGRP, somatostatin) involved in nociceptive processing at the level of the spinal cord dorsal horn/nucleus caudalis of the trigeminal nerve in CTH. Such central changes might be pathophysiologically important or merely secondary to other more important occurrences. The lack of changes in neuropeptide concentrations during drug treatment makes planning of studies involving CSF analysis easier, but also limits the probability of obtaining information on specific neuropeptide systems through CSF analysis.