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1.
J Headache Pain ; 25(1): 92, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834953

ABSTRACT

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a debilitating condition characterized by increased intracranial pressure often presenting with chronic migraine-like headache. Calcitonin gene-related peptide (CGRP) plays an important pathophysiological role in primary headaches such as migraine, whilst its role in IIH has not yet been established. METHODS: This longitudinal exploratory study included patients with IIH, episodic migraine (EM) in a headache-free interval and healthy controls (HC). Blood samples were collected from a cubital vein and plasma CGRP (pCGRP) levels were measured by standardized ELISA. RESULTS: A total of 26 patients with IIH (mean age 33.2 years [SD 9.2], 88.5% female, median BMI 34.8 kg/m2 [IQR 30.0-41.4]), 30 patients with EM (mean age 27.6 years [7.5], 66.7% female) and 57 HC (mean age 25.3 years [5.2], 56.1% female) were included. pCGRP levels displayed a wide variation in IIH as well as in EM and HC on a group-level. Within IIH, those with migraine-like headache had significantly higher pCGRP levels than those with non-migraine-like headache (F(2,524) = 84.79; p < 0.001) and headache absence (F(2,524) = 84.79; p < 0.001) throughout the observation period, explaining 14.7% of the variance in pCGRP levels. CGRP measurements showed strong intraindividual agreement in IIH (ICC 0.993, 95% CI 0.987-0.996, p < 0.001). No association was found between pCGRP levels and ophthalmological parameters. CONCLUSIONS: Although interindividual heterogeneity of pCGRP levels is generally high, migraine-like headache seems to be associated with higher pCGRP levels. CGRP may play a role in the headache pathophysiology at least in a subgroup of IIH.


Subject(s)
Calcitonin Gene-Related Peptide , Migraine Disorders , Pseudotumor Cerebri , Humans , Female , Male , Adult , Calcitonin Gene-Related Peptide/blood , Pseudotumor Cerebri/blood , Migraine Disorders/blood , Longitudinal Studies , Young Adult , Biomarkers/blood
2.
Cephalalgia ; 44(5): 3331024241248203, 2024 May.
Article in English | MEDLINE | ID: mdl-38690635

ABSTRACT

BACKGROUND: Idiopathic intracranial hypertension is a secondary headache disorder potentially causing visual loss. Neurofilament light chain is a candidate, prognostic biomarker, but further studies of neuronal biomarkers are needed. Our objective was to investigate neurofilament light chain in cerebrospinal fluid (cNfL) and plasma (pNfL), amyloid-beta 42 (Aß-42), total-tau and phosphorylated-tau in cerebrospinal fluid in new-onset idiopathic intracranial hypertension. METHODS: Prospective case-control study including new-onset idiopathic intracranial hypertension and age, sex and BMI matched controls. Biomarkers were compared between patients and controls and related to papilledema, visual fields and opening pressure. RESULTS: We included 37 patients and 35 controls. Patients had higher age-adjusted cNfL (1.4 vs. 0.6 pg/mL, p-adjusted < 0.001), pNfL (0.5 vs. 0.3 pg/mL, p-adjusted < 0.001) and total-tau/Aß-42 (0.12 vs. 0.11, p-adjusted = 0.039). Significant, positive linear correlations were found between cNfL, pNfL, total-tau/Aß-42 and opening pressure. Patients with severe papilledema had elevated cNfL compared to mild-moderate papilledema (median cNfL: 4.3 pg/mL (3.7) versus 1.0 pg/mL (1.4), p-adjusted = 0.009). cNFL was inversely associated with perimetric mean deviation (r = -0.47, p-adjusted < 0.001). CONCLUSIONS: cNfL, pNfL and total-tau/Aß-42 were elevated in new-onset idiopathic intracranial hypertension. cNfL was associated with severity of papilledema and visual field defects at diagnosis. This indicates early axonal damage. Neurofilament light chain is a candidate biomarker for disease severity.


Subject(s)
Biomarkers , Neurofilament Proteins , Pseudotumor Cerebri , Humans , Female , Male , Neurofilament Proteins/cerebrospinal fluid , Neurofilament Proteins/blood , Adult , Pseudotumor Cerebri/diagnosis , Pseudotumor Cerebri/cerebrospinal fluid , Pseudotumor Cerebri/blood , Pseudotumor Cerebri/complications , Prospective Studies , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Case-Control Studies , Middle Aged , Amyloid beta-Peptides/cerebrospinal fluid , Amyloid beta-Peptides/blood , Peptide Fragments/blood , Peptide Fragments/cerebrospinal fluid , tau Proteins/cerebrospinal fluid , tau Proteins/blood
3.
Fluids Barriers CNS ; 20(1): 3, 2023 Jan 11.
Article in English | MEDLINE | ID: mdl-36631830

ABSTRACT

BACKGROUND: Impaired cerebrospinal fluid (CSF) homeostasis is central to the pathogenesis of idiopathic intracranial hypertension (IIH), although the precise mechanisms involved are still not completely understood. The aim of the current study was to assess the CSF/serum ratio of neurofilament light chain levels (QNfL) as a potential indicator of functional CSF outflow obstruction in IIH patients. METHODS: NfL levels were measured by single molecule array in CSF and serum samples of 87 IIH patients and in three control groups, consisting of 52 multiple sclerosis (MS) patients with an acute relapse, 21 patients with an axonal polyneuropathy (PNP), and 41 neurologically healthy controls (HC). QNfL was calculated as the ratio of CSF and serum NfL levels. Similarly, we also assessed the CSF/serum ratio of glial fibrillary acidic protein (QGFAP) levels to validate the QNfL data. Routine CSF parameters including the CSF/serum albumin ratio (QAlb) were determined in all groups. Lumbar puncture opening pressure of IIH patients was measured by manometry. RESULTS: CSF-NfL levels (r = 0.29, p = 0.008) and QNfL (0.40, p = 0.0009), but not serum NfL (S-NfL) levels, were associated with lumbar puncture opening pressure in IIH patients. CSF-NfL levels were increased in IIH patients, MS patients, and PNP patients, whereas sNfL levels were normal in IIH, but elevated in MS and PNP. Remarkably, QNfL (p < 0.0001) as well as QGFAP (p < 0.01) were only increased in IIH patients. QNfL was positively correlated with CSF-NfL levels (r = 0.51, p = 0.0012) and negatively correlated with S-NfL levels (r = - 0.51, p = 0.0012) in HC, while it was only positively associated with CSF-NfL levels in IIH patients (r = 0.71, p < 0.0001). An increase in blood-CSF barrier permeability assessed by QAlb did not lead to a decrease in QNfL in any cohort. CONCLUSIONS: The observed elevation of QNfL in IIH patients, which was associated with lumbar puncture opening pressure, indicates a reduced NfL transition from the CSF to serum compartment. This supports the hypothesis of a pressure-dependent CSF outflow obstruction to be critically involved in IIH pathogenesis.


Subject(s)
Neurofilament Proteins , Pseudotumor Cerebri , Humans , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Intermediate Filaments , Multiple Sclerosis/cerebrospinal fluid , Neurofilament Proteins/cerebrospinal fluid , Pseudotumor Cerebri/blood , Pseudotumor Cerebri/cerebrospinal fluid , Spinal Puncture
4.
Int J Neurosci ; 131(8): 775-779, 2021 Aug.
Article in English | MEDLINE | ID: mdl-32303142

ABSTRACT

AIM: Idiopathic intracranial hypertension (IIH), a disease of obscure origin, is characterized by headache and visual disturbances due to increased intracranial pressure. Recent line of evidence has suggested involvement of inflammation in IIH pathogenesis thus bringing forward anti-glial autoimmunity as a potential contributor of IIH. Glial fibrillary acidic protein (GFAP) is a major astrocytic autoantigen associated with a specific form of meningoencephalitis. MATERIALS AND METHODS: In this study, we investigated the presence of GFAP-antibody in 65 sera (49 obtained during active disease and 16 during remission) and in 15 cerebrospinal fluid (CSF) samples of 58 consecutively recruited IIH patients using cell based assay and indirect immunohistochemistry. RESULTS: GFAP-antibody was found in active period sera of 2 IIH patients with classical symptoms and good treatment response. Two remission period sera obtained at different time points from one of these cases showed lower titers of GFAP-antibody positivity. IgG from positive samples yielded an astrocytic immunoreactivity pattern. None of the CSF samples showed GFAP-antibodies. CONCLUSIONS: These results suggest that anti-astrocyte autoimmunity might be present in a fraction of IIH patients. Exact pathogenic significance of this association needs to be further studied.


Subject(s)
Glial Fibrillary Acidic Protein/blood , Glial Fibrillary Acidic Protein/immunology , Pseudotumor Cerebri/blood , Pseudotumor Cerebri/immunology , Adult , Autoantibodies/blood , Female , Humans , Male , Pseudotumor Cerebri/cerebrospinal fluid
5.
Neurol Sci ; 38(10): 1817-1822, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28733756

ABSTRACT

Headache and visual disturbances are the main presenting symptoms of idiopathic intracranial hypertension (IIH) characterized by increased intracranial pressure (ICP) with an unknown cause. We aimed to investigate the antibodies against optic neuritis-associated glial antigens, aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) and uncharacterized neuronal membrane antigens in IIH patients. Consecutive patients diagnosed according to Friedman revised diagnostic criteria and control subjects were included after their consent. All serum samples were analyzed for antibodies against AQP4 and MOG using cell-based immunofluorescent assays and for uncharacterized neuronal membrane antigens by indirect immunocytochemistry utilizing live neurons. Sera of 34 patients with IIH and 40 control subjects were investigated but none of the patients showed AQP4 and MOG antibodies. However, serum IgG of five IIH patients showed reactivity against membrane antigens of rat hippocampal and cortical neurons. Interestingly, three out of these five patients had nonspecific white matter lesions on MRI, whereas only four of all other patients had these lesions (p = 0.048). AQP4 and MOG antibodies do not seem to have a role in the pathophysiology of IIH. However, association of immunocytochemistry findings with the presence of white matter lesions may suggest that immunological factors contribute to the pathogenesis of IIH in at least some of the patients.


Subject(s)
Autoantibodies/blood , Nerve Tissue Proteins/immunology , Pseudotumor Cerebri/blood , Pseudotumor Cerebri/immunology , Adult , Biomarkers/blood , Brain/diagnostic imaging , Brain/immunology , Brain/pathology , Cells, Cultured , Female , Follow-Up Studies , Humans , Male , Multiple Sclerosis/blood , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/immunology , Multiple Sclerosis/pathology , Neuroglia/immunology , Neuroglia/pathology , Neurons/immunology , Neurons/pathology , Pseudotumor Cerebri/diagnostic imaging , Pseudotumor Cerebri/pathology
6.
Acta Neurol Belg ; 117(3): 707-711, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28220397

ABSTRACT

Although formerly considered as a "benign" disease, the presence of some important problems such as vision loss, resistance to appropriate medical treatment and relapses suggests that neuronal damage might play a role in the pathophysiology of IIH. In order to demonstrate possible neuronal damage/dysfunction participating in IIH pathophysiology, we aimed to investigate the relationship between serum neuron-specific enolase (NSE) levels and clinical features in patients with idiopathic intracranial hypertension (IIH). Thirty-six patients with IIH, diagnosed according to the revised criteria, and 40 age, gender and body mass index-matched healthy controls were enrolled in this study after their consent. Serum samples were evaluated for NSE via enzyme-linked immunosorbent assay method. NSE levels were higher in the IIH group (23.7 ± 14.53 ng/ml) compared to the control group (22.7 ± 13.11 ng/ml), but the difference was not statistically significant (p = 0.824). There were also no statistically significant differences in NSE levels in IIH patients regarding the presence of visual loss, relapse, oligoclonal bands and papilledema. We could not demonstrate any correlations between NSE levels and age, body mass index, cerebrospinal fluid opening pressure and disease duration. The present study is the first to analyze NSE levels in IIH patients and showed no significant difference between patients and controls, and also between different clinical subgroups of IIH patients.


Subject(s)
Neurons/enzymology , Phosphopyruvate Hydratase/blood , Pseudotumor Cerebri/blood , Pseudotumor Cerebri/physiopathology , Adult , Biomarkers/blood , Female , Humans , Male , Middle Aged
7.
Cephalalgia ; 37(6): 525-531, 2017 May.
Article in English | MEDLINE | ID: mdl-27193133

ABSTRACT

Background Although specific role players are currently unknown, contribution of inflammatory mediators has been suggested in the pathophysiology of idiopathic intracranial hypertension (IIH), which is a disease more prevalent in obese female individuals of childbearing age. We aimed to investigate the levels of adipokines and cytokines to demonstrate possible markers for inflammation that participate in IIH pathophysiology and their association with clinical features of IIH. Methods IIH patients, diagnosed according to the revised criteria, and age-, gender- and body mass index (BMI)-matched healthy controls were enrolled in this study. Serum samples were evaluated for insulin-like growth factor 1, insulin, nesfatin, adiponectin, interleukin (IL)-1ß, IL-6, IL-8, leptin, plasminogen activator inhibitor type-1, resistin, tumour necrosis factor-alpha (TNF-α) and monocyte chemotactic protein 1 via enzyme-linked immunosorbent assay or multiplex immunoassays. Results IL-1ß level was significantly higher ( p = 0.012), and IL-8 and TNF-α levels were significantly lower in the IIH group ( p < 0.001 and p = 0.008, respectively) compared to the control group. There were no correlations between the cytokine/adipokine levels and age, BMI, disease duration, and cerebrospinal fluid oligoclonal bands. There were also no significant differences in cytokine and adipokine levels between IIH patients regarding visual impairment. However, statistically significant differences were found between IIH patients with relapse versus healthy controls regarding IL-1ß ( p = 0.007), IL-8 ( p = 0.001) and TNF-α ( p = 0.017) levels. Other investigated cytokines and adipokines showed no significant alterations in IIH patients investigated in the remission period. Conclusion Altered serum levels of IL-1ß, IL-8 and TNF-α seem to be associated with IIH pathogenesis, and these cytokines may be used as prognostic markers in IIH to predict relapse.


Subject(s)
Adipokines/blood , Inflammation Mediators/blood , Pseudotumor Cerebri/blood , Pseudotumor Cerebri/diagnostic imaging , Adult , Biomarkers/blood , Female , Humans , Magnetic Resonance Angiography/methods , Magnetic Resonance Imaging/methods , Male , Middle Aged
8.
J Neurol Sci ; 372: 78-84, 2017 Jan 15.
Article in English | MEDLINE | ID: mdl-28017254

ABSTRACT

INTRODUCTION: Vitamin A and its metabolites (called retinoids) have been thought to play a role in the development of idiopathic intracranial hypertension (IIH). The IIH Treatment Trial (IIHTT) showed the efficacy of acetazolamide (ACZ) in improving visual field function, papilledema grade, quality of life and cerebrospinal fluid (CSF) pressure. We postulated that IIH patients would demonstrate elevated measures of vitamin A metabolites in the serum and CSF. METHODS: Comprehensive measures of serum vitamin A and its metabolites were obtained from 96 IIHTT subjects, randomly assigned to treatment with ACZ or placebo, and 25 controls with similar gender, age and body mass index (BMI). These included retinol, retinol binding protein, all-trans retinoic acid (ATRA), alpha- and beta-carotenes, and beta-cryptoxanthin. The IIHTT subjects also had CSF and serum vitamin A and metabolite measurements obtained at study entry and at six months. RESULTS: At study entry, of the vitamin A metabolites only serum ATRA was significantly different in IIHTT subjects (median 4.33nM) and controls (median 5.04nM, p=0.02). The BMI of IIHTT subjects showed mild significant negative correlations with serum ATRA, alpha- and beta-carotene, and beta-cryptoxanthin. In contrast, the control subject BMI correlated only with serum ATRA. At six months, the serum retinol, alpha-carotene, beta-carotene, and CSF retinol were increased from baseline in the ACZ treated group, but only increases in alpha-carotene (p=0.02) and CSF ATRA (p=0.04) were significantly greater in the ACZ group compared with the placebo group. No other vitamin A measures were significantly altered over the six months in either treatment group. Weight loss correlated with only with the change in serum beta-carotene (r=-0.44, p=0.006) and the change in CSF retinol (r=-0.61, p=0.02). CONCLUSION: Vitamin A toxicity is unlikely a contributory factor in the causation of IIH. Our findings differ from those of prior reports in part because of our use of more accurate quantitative methods and measuring vitamin A metabolites in both serum and CSF. ACZ may alter retinoid metabolism in IIH patients.


Subject(s)
Pseudotumor Cerebri/blood , Vitamin A/blood , Acetazolamide/therapeutic use , Adult , Anticonvulsants/therapeutic use , Carotenoids/metabolism , Chromatography, High Pressure Liquid , Chromatography, Liquid , Female , Follow-Up Studies , Humans , Male , Mass Spectrometry , Obesity/metabolism , Pseudotumor Cerebri/cerebrospinal fluid , Pseudotumor Cerebri/complications , Pseudotumor Cerebri/drug therapy , Retinol-Binding Proteins/metabolism , Tretinoin/blood , Visual Fields/drug effects , Vitamin A/cerebrospinal fluid , Young Adult
9.
Headache ; 53(10): 1666-9, 2013.
Article in English | MEDLINE | ID: mdl-24266338

ABSTRACT

We offer for consideration a possible association between hypermobility syndrome seen in Ehlers-Danlos syndrome and risk of potential development of idiopathic intracranial hypertension - mediated primarily through the effects of insulin-like growth factor-1.


Subject(s)
Ehlers-Danlos Syndrome/blood , Ehlers-Danlos Syndrome/diagnosis , Insulin-Like Growth Factor I/metabolism , Pseudotumor Cerebri/blood , Pseudotumor Cerebri/diagnosis , Adult , Female , Humans
10.
Curr Eye Res ; 38(9): 972-6, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23713489

ABSTRACT

PURPOSE: Previous reports have connected between Idiopathic intracranial hypertension (IIH), obesity and different hormonal states. The aim of this study was to characterize the endocrine profile in women with IIH. METHODS: This is a data-based study of 51 IIH patients. We measured anthropometric parameters and assessed hormonal profile including cortisol, testosterone, bioavailable testosterone (BT), prolactin, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, insulin, aldosterone, estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Pearson or Spearman rank correlation for non-normally distributed variables were calculated to evaluate the relation among the anthropometric measurements: age, body mass index (BMI), waist and hip circumference and waist to hip ratio (WHR) with hormones levels. RESULTS: Seventy-eight percent of the cohort had WHR < 0.85 and 21.6% had a WHR > 0.85. Increased levels of testosterone, BT and androstenedione were all positively related to younger age of diagnosis in patient who are diagnosed after the age of 25 (R = -1.066, -0.845, -0.735, p < 0.001, =0.024, 0.019, respectively). No correlation was found between any of the analyzed hormones and the duration of the disease, WHR or BMI, except insulin, which was positively related to BMI (R = 0.461, p = 0.001). CONCLUSIONS: Increased levels of circulating androgens are associated with earlier age of onset of IIH in women.


Subject(s)
Hyperandrogenism/blood , Hyperandrogenism/complications , Obesity/complications , Pseudotumor Cerebri/blood , Pseudotumor Cerebri/complications , Adolescent , Adult , Age of Onset , Aldosterone/blood , Androstenedione/blood , Body Fat Distribution , Dehydroepiandrosterone Sulfate/blood , Estradiol/blood , Female , Follicle Stimulating Hormone, Human/blood , Humans , Hydrocortisone/blood , Insulin/blood , Luteinizing Hormone/blood , Middle Aged , Obesity/metabolism , Prolactin/blood , Testosterone/blood , Young Adult
11.
Am J Med Sci ; 346(3): 194-8, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23187300

ABSTRACT

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a syndrome consisting of headache, visual field defects and papilledema of uncertain etiology. The prospect was raised previously as to an association between aldosteronism and increased intracranial pressure in 2 middle-aged women with IIH and primary aldosteronism (PAL). Since then, 2 additional adults were identified and 2 other cases were reported from the United Kingdom, whereas 6 cases of IIH and secondary aldosteronism (SAL) in children have been reported in the English literature worldwide. METHODS: A retrospective analysis of cases from author institutions and published literature comparing clinical features, laboratory findings and therapeutic interventions in these 12 cases. RESULTS: The female-to-male ratio was 10:2. The mean age of the PAL patients was 49 ± 3 years-all hypertensive, with adrenal pathology in most. The mean age of the SAL patients was 11 ± 2 years-mostly normotensive, with 3 having Bartter's and 2 Gitelman syndromes, and 1 renal congenital hypoplasia. Plasma aldosterone levels were elevated (31 ± 5 ng/dL) in PAL and SAL, whereas plasma renin activity was suppressed in PAL. Hypokalemia (3.2 ± 0.2 mmol/L), hypomagnesemia (1.6 ± 0.3 mg/dL) and a putative metabolic alkalosis (serum HCO3 30 ± 1 mmol/L) were observed. IIH symptoms were controlled by spironolactone in 5, amiloride in 1, correction of hypokalemia and hypomagnesemia in 2, discontinuation of nonsteroidal anti-inflammatory drugs in 2, and reduction of body weight in 1. One patient required serial lumbar punctures, 2 a ventriculoperitoneal shunt, whereas all 3 patients with adrenal adenoma underwent surgical resection. CONCLUSIONS: An association between IIH and PAL occurs in hypertensive middle-aged women, whereas normotensive girls having an inherited renal tubular defect may have IIH with SAL. Patients with IIH should be evaluated for aldosteronism and considered for spironolactone therapy.


Subject(s)
Hyperaldosteronism/complications , Pseudotumor Cerebri/etiology , Adolescent , Adult , Aldosterone/blood , Child , Electrolytes/blood , Female , Humans , Hyperaldosteronism/blood , Hyperaldosteronism/drug therapy , Male , Middle Aged , Mineralocorticoid Receptor Antagonists/therapeutic use , Pseudotumor Cerebri/blood , Renin/blood , Spironolactone/therapeutic use
12.
Cephalalgia ; 32(3): 198-202, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22238356

ABSTRACT

OBJECTIVES: We aimed to investigate anti-aquaporin-4 (AQP-4) water channel antibodies, affecting cerebrospinal fluid (CSF) secretion and absorption, in idiopathic intracranial hypertension (IIH) patients. METHODS: Patients fulfilling the modified Dandy's diagnostic criteria for IIH were included and their clinical features and CSF findings were reviewed. Their serum samples and control groups were investigated by immunofluorescence and a cell-based assay for anti-AQP-4 antibodies and by immunohistochemistry for IgG binding patterns. RESULTS: Twenty-nine patients diagnosed with IIH were investigated. We could not detect any anti-AQP-4 antibodies in our series. However, we identified different serum IgG binding patterns in 11 IIH patients. CONCLUSION: There is only one report investigating the anti-AQP4 antibodies in IIH. Our study with a larger sample confirmed the results of this report and indicated that AQP4 antibodies did not have a primary role in IIH pathogenesis, but provided some support for the contribution of inflammatory mechanisms in IIH.


Subject(s)
Aquaporin 4/immunology , Autoantibodies/blood , Pseudotumor Cerebri/immunology , Adolescent , Adult , Aged , Autoantigens/immunology , Female , Fluorescent Antibody Technique , Humans , Male , Middle Aged , Pseudotumor Cerebri/blood , Young Adult
13.
Regul Pept ; 164(2-3): 71-7, 2010 Sep 24.
Article in English | MEDLINE | ID: mdl-20553977

ABSTRACT

Idiopathic intracranial hypertension is a disorder of unknown pathogenesis. Natriuretic peptides may be involved in intracranial pressure regulation, but cerebrospinal fluid (CNS) and plasma concentrations in this disorder are unknown. We evaluated venous and intrathecal concentrations of ANP, BNP and CNP precursor peptides in 40 patients with idiopathic intracranial hypertension and in 20 controls. Natriuretic pro-peptides were quantitated using processing-independent assays. In CSF, no differences in peptide concentrations between patients and controls were found (proANP: 239 + or - 23 vs 231 + or - 22 pmol/L, proBNP: <2 pmol/L in all, proCNP: 1079 + or - 318 vs 1138 + or - 323 pmol/L). In plasma, proCNP was lower in IIH compared with controls (35.3 + or - 4.8 pmol/L vs 43.8 + or - 5.9 pmol/L, p<0.0001). Moreover, plasma proBNP was significantly lower in patients compared with controls (47.1 + or -21.4 pmol/L vs 59.2 + or - 22.0 pmol/L, p = 0.045). There were no associations between peptide concentrations and ICP and BMI, respectively. Plasma proANP and proCNP increased during 3 months follow-up (p=0.01 and p=0.006), n=12. We suggest that decreased plasma proCNP concentration in idiopathic intracranial hypertension may reflect endothelial dysregulation of vascular tone and may be a marker in this disease. Further studies of proCNP and endothelial function are needed to establish such role.


Subject(s)
Natriuretic Peptides/blood , Natriuretic Peptides/cerebrospinal fluid , Pseudotumor Cerebri/blood , Pseudotumor Cerebri/cerebrospinal fluid , Adult , Atrial Natriuretic Factor/blood , Atrial Natriuretic Factor/cerebrospinal fluid , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Natriuretic Peptide, Brain/cerebrospinal fluid , Natriuretic Peptide, C-Type/blood , Natriuretic Peptide, C-Type/cerebrospinal fluid , Young Adult
14.
Blood Coagul Fibrinolysis ; 21(4): 328-33, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20400894

ABSTRACT

Several studies have suggested that thrombophilic risk factors are more prevalent in individuals with idiopathic intracranial hypertension (IIH), and that a prothrombic state may be involved in the etiopathogenesis of this disease. We examine thrombophilic factors in a group of patients with IIH in relation to obesity. In addition, we reviewed the relevant literature and performed a meta-analysis. Thrombophilia work-up was performed on 51 patients with IIH at least 1 month following their first episode. Samples for the analysis of factor V Leiden (FVL), prothrombin gene variant (PGV) G20210A and methylenetetrahydrofolate reductase (MTHFR) were available in an additional 30 patients, that is 81 patients in all. Meta-analysis was performed. Of the 51 patients 40 were obese. Increased concentrations of fibrinogen, D-Dimer, factor VIII, factor IX and factor XI were found in 15, 7, 7, 6 and 2 patients, respectively, all obese. The circulating anticoagulant, measured by dilute Russell's viper venom time (dRVVT assay), found mainly in obese. All 51 patients were negative for the anticardiolipin antibody (IgG immunoglobulin G) and IgG anti-beta2 glycoprotein I. In the meta-analysis antiphospholipid antibodies were significantly associated with IIH [odds ratio (OR) of 4.25 (1.68-12.60)], similar to the association with high factor VIII [OR = 16.17 (2.87-91.01)], higher plasminogen activator inhibitor-1 (PAI-1) levels [OR = 6.91 (2.28-20.91)], and high lipoprotein (a) [LP(a)] [OR = 3.54 (1.54-8.70)]. Obesity often observed in IIH patients is frequently linked with thrombophilic factors. Thus, we believe that dysmetabolism could be the thrombophilic target for treatment in patients with IIH.


Subject(s)
Obesity/complications , Pseudotumor Cerebri/blood , Pseudotumor Cerebri/complications , Thrombophilia/complications , Adult , Antibodies, Antiphospholipid/blood , Factor V/genetics , Factor VIII/metabolism , Female , Fibrinolysis , Genetic Variation , Humans , Lipoprotein(a)/blood , Male , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Middle Aged , Prothrombin/genetics , Pseudotumor Cerebri/etiology , Risk Factors , Young Adult
17.
Headache ; 49(2): 282-5, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19222599

ABSTRACT

BACKGROUND: The pathogenesis of idiopathic intracranial hypertension (IIH) remains unclear and as such it remains a diagnosis of exclusion. OBJECTIVES: To identify cerebrospinal fluid (CSF) and serum cytokine and chemokine profiles associated with IIH. METHOD: Semiquantitative assessment with cytokine antibody arrays was used to detect the relative expression of 42 different cytokines and chemokines in the CSF and serum of 8 IIH patients and 8 controls. Subsequently, quantitative assay with enzyme linked immunosorbent assay was performed for chemokine CCL2, interleukin-1 alpha (IL-1alpha), and leptin. RESULTS: Cytokine antibody array showed elevated levels of CCL2 in the CSF and CCL7, CCL8, IL-1alpha, and leptin levels in serum in IIH patients compared with controls. Subsequent quantitative assessment with enzyme linked immunosorbent assay showed significantly elevated CSF CCL2 in IIH patients compared with controls (P < .01) but there was no significant difference in leptin and IL-1alpha levels between the groups. CONCLUSION: This is the first report demonstrating differences in cytokine expression in the serum and CSF in IIH patients compared with controls. Since the pathogenesis of IIH is unclear, the heterogeneity of the cytokine expression reported here may help understand the pathogenesis of this condition.


Subject(s)
Chemokines/metabolism , Cytokines/metabolism , Pseudotumor Cerebri/blood , Pseudotumor Cerebri/cerebrospinal fluid , Adolescent , Adult , Aged , Chemokines/analysis , Cytokines/analysis , Enzyme-Linked Immunosorbent Assay , Female , Humans , Middle Aged
18.
Clin Endocrinol (Oxf) ; 70(6): 863-9, 2009 Jun.
Article in English | MEDLINE | ID: mdl-18771566

ABSTRACT

OBJECTIVE: The aetiology of idiopathic intracranial hypertension (IIH) is not known, but its association with obesity is well-recognized. Recent studies have linked obesity with abnormalities in circulating inflammatory and adiposity related cytokines. The aim of this study was to characterize adipokine and inflammatory cytokine profiles in IIH. DESIGN: Paired serum and cerebrospinal fluid (CSF) specimens were collected from 26 patients with IIH and compared to 62 control subjects. Samples were analysed for leptin, resistin, adiponectin, insulin, IL-1beta, IL-6, IL-8 (CXCL8), TNFalpha, MCP-1 (CCL2), hepatocyte growth factor, nerve growth factor and PAI-1 using multiplex bead immunoassays. RESULTS: CSF leptin was significantly higher in patients with IIH (P = 0.001) compared to controls after correction for age, gender and body mass index (BMI). In the control population, BMI correlated with serum leptin (r = 0.34; P = 0.007) and CSF leptin (r = 0.51; P < 0.0001), but this was not the case for the IIH population. Profiles of other inflammatory cytokines and adipokines did not differ between IIH patients and controls once anthropometric factors had been accounted for. CONCLUSIONS: IIH was characterized by significantly elevated CSF leptin levels which did not correlate with BMI. We suggest that CSF leptin may be important in the pathophysiology of IIH and that obesity in IIH may occur as a result of hypothalamic leptin resistance.


Subject(s)
Drug Resistance , Hypothalamus/physiopathology , Leptin/cerebrospinal fluid , Pseudotumor Cerebri/physiopathology , Adipokines/blood , Adipokines/cerebrospinal fluid , Adult , Body Mass Index , Case-Control Studies , Cytokines/blood , Cytokines/cerebrospinal fluid , Female , Humans , Hypothalamus/drug effects , Leptin/blood , Middle Aged , Pseudotumor Cerebri/blood , Pseudotumor Cerebri/cerebrospinal fluid
19.
J Neuroophthalmol ; 27(4): 258-62, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18090557

ABSTRACT

BACKGROUND: Several studies have implicated vitamin A-related compounds in the pathogenesis of idiopathic intracranial hypertension (IIH). The goal of this study was to compare cerebrospinal fluid (CSF) and serum concentrations of retinol and retinol-binding protein (RBP) in subjects with and without IIH. METHODS: CSF and serum samples were collected from 87 subjects. The study population was composed of subjects with IIH (IIH group, n = 28), subjects with non-IIH neurologic conditions (neurology controls, n = 42), and subjects undergoing preoperative lumbar puncture but with no known neurologic conditions (anesthesia controls, n = 17). RBP levels (nM) were determined using radial immunodiffusion, and retinol levels (nM) were determined using high-performance liquid chromatography. RESULTS: The retinol/RBP ratio was greater in CSF than in serum, especially in subjects with IIH. CONCLUSIONS: The finding of increased levels of unbound retinol in the CSF of subjects with IIH provides further evidence that vitamin A may be involved in the pathogenesis of IIH. Comparative statistical analyses revealed multivariate relationships that demonstrate the need to further investigate correlations between vitamin A and RBP levels in CSF and serum.


Subject(s)
Pseudotumor Cerebri/blood , Pseudotumor Cerebri/cerebrospinal fluid , Retinol-Binding Proteins/metabolism , Vitamin A/blood , Vitamin A/cerebrospinal fluid , Adult , Chromatography, High Pressure Liquid/methods , Female , Humans , Linear Models , Male , Radioimmunoassay/methods , Spectrum Analysis
20.
Thromb Haemost ; 96(4): 483-7, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17003926

ABSTRACT

It was the objective of this study to explore the possibility that the aggregation of red blood cells is enhanced in individuals with increased intracranial hypertension (IIH). This is a prospective cross sectional examination in a cohort of patients with IIH and matched controls. The aggregation of red blood cells in the peripheral venous blood was determined by using a slide test and image analysis. We have presently included a group of 33 women with IIH and the same number of women matched for age, body mass index, vascular risk factors and medications. A significant (p = 0.038) increment in fibrinogen concentrations was noted in the patients (341 +/- 60.8 mg/dl) as opposed to the controls 307.9 +/- 64.8). The same stands for the aggregation of red blood cells (aggregation parameter of 8.7 +/- 4.9 in patients vs.5.9 +/- 3.2 in the controls, p = 0.001). We noted an increment in the aggregation of red blood cells in the peripheral blood of 33 women with IIH as opposed to matched controls. Being associated with capillary slow flow, these findings might be relevant to the ethiopathogenesis of this disease.


Subject(s)
Erythrocyte Aggregation , Fibrinogen/metabolism , Pseudotumor Cerebri/blood , Adolescent , Adult , Blood Sedimentation , Body Mass Index , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Middle Aged , Prospective Studies
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