Role of inflammatory markers in the assessment of meningitis in adult patients with fever and headache.

BACKGROUND: Meningitis, especially of bacterial origin, is a medical emergency that must be diagnosed promptly. However, due to the associated risks of complications of lumbar puncture, it is crucial to identify individuals who truly need it. The aim of this study was to assess the diagnostic role of inflammatory markers in distinguishing among patients without meningitis, those with aseptic meningitis, and those with bacterial meningitis. METHODS: This was a retrospective, diagnostic study at an acute care hospital, involving adult patients who presented to either ambulatory care or the emergency department with fever and headache, but without altered mental status or neurological deficits. Inflammatory markers (C-reactive protein [CRP], mean platelet volume, neutrophil-lymphocyte ratio, and red cell distribution width) were assessed as index tests. An expert panel classified patients into three groups: no meningitis, aseptic meningitis, and bacterial meningitis using predefined criteria. RESULTS: Of the 80 patients, 52 had no meningitis, 27 had aseptic meningitis, and 1 had bacterial meningitis. Of the inflammatory markers investigated, only CRP showed potential usefulness in differentiating these three diagnostic groups, with median values of 5.6 (interquartile range [IQR] 2.1, 11.3) mg/dL in those without meningitis, 0.2 (IQR 0.1, 1.2) mg/dL in those with aseptic meningitis, and notably elevated at 21.7 mg/dL in the patient with bacterial meningitis. CONCLUSION: In adult patients presenting with fever and headache in an emergency setting, CRP was the only marker that demonstrated potential diagnostic utility in distinguishing among those with no meningitis, aseptic meningitis, and bacterial meningitis.

Effect of fasting-induced headache on calcitonin gene related peptide (CGRP) and other clinical biomarkers on the first day of Ramadan: Sub-analysis from a randomized open label clinical trial.

BACKGROUND: Fasting-induced headaches (FIHs) have been shown to occur on the first day of Ramadan and clearly decline thereafter. Despite the wealth of knowledge about different types of headaches (e.g., migraine-, cluster-, and tension-type headaches), research on the mechanism underlying FIHs, as well as their treatment, remains scarce. Our study aimed to investigate any association between FIHs during the first day of Ramadan and potential headache-related biomarkers, including fasting blood glucose (FBG), C-reactive protein (CRP), magnesium, vitamin B9, vitamin B12, homocysteine, and calcitonin gene related peptide (CGRP), and to assess whether a prophylactic use of paracetamol may influence these biomarkers. METHODS: As part of a randomized, open-label clinical trial that evaluated the effect of paracetamol as a prophylactic therapy for FIH, blood samples from stratified subjects in the prophylaxis and control groups were withdrawn while fasting after the 1st dose of paracetamol (in the prophylaxis group) and prior to reporting headache occurrence. RESULTS: Plasma and serum were separated for 61 subjects; 31 and 30 subjects from the prophylaxis and control groups, respectively. Overall, no significant differences were found in the levels of FBG, CRP, magnesium, vitamin B9, and vitamin B12 in headache-suffering subjects compared to those without headache despite the use of paracetamol for prophylaxis. Homocysteine, however, was significantly reduced in all subjects who experienced FIH compared to those without headache (median 6.9 [1.6] vs. 7.7 [2.7] umol/L; p = 0.041). On the contrary, when the CGRP was measured using immunoassay, it was found to be significantly elevated in all headache-suffering subjects compared to those without headache (median 126.1 [17.7] vs. 105.8 [19.6] pg/mL; p ≤ 0.0001). This difference was maintained upon comparing the headache to non-headache subjects in both the prophylaxis (median 121.5 [15.4] vs. 105.8 [9.4] pg/mL; p < 0.01) and control groups (median 128.5 [28.3] vs. 105.8 [23.8] pg/mL; p < 0.01). Additionally, an elevated CGRP level was found to increase the odds of having a FIH [OR = 1.32; 95%CI 1.06-1.22]. CONCLUSIONS: Our findings revealed the role of CGRP in FIHs for the first time and suggest further investigation in signaling pathways downstream CGRP receptors. Furthermore, the modulation CGRP or CGRP receptors could have a clinical application in the prevention of FIHs. TRIAL REGISTRATION: This study was registered with the Saudi Food and Drug Authority in the Saudi Clinical Trials Registry (SCTR; No. 22122102).

Occurrence of new or more severe headaches following COVID-19 is associated with markers of microglial activation and peripheral sensitization: results from a prospective cohort study.

BACKGROUND: New onset or worsening of a headache disorder substantially contributes to the disease burden of post-COVID-19. Its management poses a suitable means to enhance patients' participation in professional, social, and personal activities. Unfortunately, the pathophysiology of post-COVID-19 headaches is poorly understood. This study aims to investigate the role of (neuro-) inflammatory mechanisms in order to guide the development of anti-inflammatory treatment strategies. METHODS: We included patients from the interdisciplinary post-COVID-19 Rehabilitation Study (PoCoRe, n = 184 patients) run at a tertiary care university hospital, comprising patients with PCR-confirmed SARS-CoV-2 infection ≥ 6 weeks prior to their initial consultation. Patients reporting any headache since their infection were considered for this study (n = 93). These were interviewed and classified according to the International Classification of Headache Disorders, Third Edition (ICHD-3) by headache specialists. Patient sera were additionally analysed for levels of VILIP-1, MCP-1 (CCL2), sTREM-2, BDNF, TGF-ß1, VEGF, IL-6, sTREM-1, ß-NGF, IL-18, TNF-alpha, sRAGE, and CX3CL1 (Fractalkine). Markers of inflammation were compared between four groups of patients (none, unchanged, worsened, or new headache disorder). RESULTS: Patients reported experiencing more severe headaches (n = 17), new onset headaches (n = 46), unchanged headaches (n = 18), and surprisingly, some patients denied having any headaches (n = 12) despite self-reports. Serum levels of CX3CL1 were increased in the worsened (2145 [811-4866] pg/ml) and new onset (1668 [0-7357] pg/ml) headache group as compared to patients with no (1129 [0-5379] pg/ml) or unchanged (1478 [346-4332] pg/ml) headaches. Other markers also differed between groups, but most significantly between patients with worsened (TGF-ß1: 60 [0-310] pg/ml, VEGF: 328 [86-842] pg/ml, ß-NGF: 6 [3-38] pg/ml) as compared to unchanged headaches (TGF-ß1: 29 [0-77] pg/ml, VEGF: 183 [72-380] pg/ml, ß-NGF: 3 [2-89] pg/ml). The results did not differ between headache phenotypes. DISCUSSION: This study provides evidence that worsened or new headaches following COVID-19 are associated with pro-(neuro-)inflammatory profiles. This supports the use of anti-inflammatory treatment options in this population, especially in the subacute phase.

Effects of endurance exercise on serum concentration of calcitonin gene-related peptide (CGRP): a potential link between exercise intensity and headache.

Background Calcitonin gene-related peptide (CGRP) is a powerful neuropeptide that is strongly involved in headache pain pathogenesis by triggering vasodilation, mast cell degranulation and neurogenic inflammation. This evidence has prompted us to investigate the acute influence of endurance exercise on CGRP concentration in blood. Methods The study population consisted of 48 male amateur runners, who ran a half-marathon distance at 75%-85% of maximal oxygen uptake. Blood was drawn before the run (pre-run) and immediately after each runner ended his trial (post-run). The serum concentration of CGRP was measured with a commercial enzyme-linked immunosorbent assay (ELISA) technique. Results Overall, 22/48 subjects (45.8%) reported suffering from headache, three of whom (6.2%) had an exertional headache, whilst 26/48 (54.2%) subjects did not report at least one headache episode during the previous 6 months (i.e. headache-free). All 48 athletes successfully covered the 21.1 km distance. Serum concentration of CGRP significantly increased by 1.5-fold in the entire group, as well as in the headache-positive and headache-free cohorts. Univariate Spearman's correlation revealed that post-run variation of serum CGRP was significantly and inversely associated with running time (r = -0.30; p = 0.036). Conclusions The serum concentration of CGRP is significantly enhanced by medium-distance endurance exercise and the post-exercise increase is dependent on running intensity. Accordingly, high-exercise intensity might be directly related to triggering both exertional headache and/or migraine episodes.

Vitamin D3 might improve headache characteristics and protect against inflammation in migraine: a randomized clinical trial.

INTRODUCTION: Due to anti-inflammatory effects of vitamin D3, we aimed to explore the effects of supplementation with this vitamin on headache characteristics and serum levels of pro/anti-inflammatory markers in migraineurs. METHODS AND MATERIALS: This placebo-controlled, double-blind study included 80 episodic migraineurs who randomly assigned into two equal groups to receive either daily dose of vitamin D3 2000 IU (50 µg) or placebo for 12 weeks. At baseline and after the trial, headache characteristics were determined using diaries and serum levels of interleukin (IL)-10, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (Cox-2) were assessed via ELISA method. RESULTS: At the end of trial, analysis of covariance (ANCOVA) adjusted for baseline values, and confounders revealed that vitamin D3 supplemented group experienced significantly lower headache days per month (4.71), reduced attacks duration (12.99 h/attack), less severe headaches (5.47, visual analog scale), and lower analgesics use/month (2.85) than placebo group (6.43, 18.32, 6.38 and 4.87, respectively) (P values < 0.05). Using ANCOVA adjusted for baseline levels and confounding variables, it was found that serum levels of IL-10 and Cox-2 did not significantly differ between groups after the experiment; whereas, iNOS serum level was significantly reduced in the intervention group (106.06 U/L) comparing to the controls (156.18 U/L P : 0.001). Also, the patients receiving vitamin D3 yielded a marginally significant lower IL-6 serum concentration (76.43 ng/L) compared to placebo (93.10 ng/L) (P value:0.055). CONCLUSION: Based on the results of this study, we found that 2000 IU (50 µg)/day vitamin D3 supplementation for 12 weeks could improve headache characteristics and might reduce neuro-inflammation in episodic migraine.

Intrinsic Coagulation Pathway, History of Headache, and Risk of Ischemic Stroke.

Background and Purpose- Hypercoagulable states in migraine patients may play a role in the pathophysiology underlying the association between migraine and ischemic stroke. This study aims to provide more insight into the potential association of headache, ischemic stroke, and the intrinsic coagulation pathway. Methods- We included patients from the RATIO study (Risk of Arterial Thrombosis in Relation to Oral Contraceptives), a Dutch population-based case-control study including young women (age <50) with ischemic stroke and healthy controls. We defined a headache group based on a questionnaire on headache history. Intrinsic coagulation proteins were measured through both antigen levels (FXII, FXI, prekallikrein, HK [high molecular weight kininogen]) and protein activation, determined by measuring activated protein complex with C1esterase-inhibitor (FXIIa-C1-INH, FXIa-C1-INH, Kallikrein-C1-INH) or antitrypsin-inhibitor (FXIa-AT-INH). We calculated adjusted odds ratios and performed an interaction analysis assessing the increase in stroke risk associated with high levels of intrinsic coagulation and history of headache. Results- We included 113 ischemic stroke cases and 598 healthy controls. In total, 134 (19%) patients had a history of headache, of whom 38 were cases and 96 controls. The combination of headache and high intrinsic coagulation protein levels (all but FXII antigen level and both FXIa-inhibitors) was associated with an increase in ischemic stroke risk higher than was expected based on their individual effects (adjusted odds ratio FXI antigen level alone: 1.7, 95% CI, 1.0-2.9; adjusted odds ratio headache alone: 2.0, 95% CI, 1.1-3.7; combination: 5.2, 95% CI, 2.3-11.6) Conclusions- Headache and high intrinsic coagulation protein levels may biologically interact, increasing risk for ischemic stroke.

A prospective study of headache and neuropeptides in patients with pituitary adenomas.

OBJECTIVE: To evaluate clinical criteria for headache associated with pituitary adenoma (HaPA) in the International Classification of Headache Disorders (ICHD) 3rd edition version criteria and further determine whether elevations of plasma calcitonin gene-related peptide and pituitary adenylate cyclase-activating peptide 1-38 (PACAP1-38) concentration contribute to HaPA. METHODS: Demographic and clinical features of consecutive patients with pituitary adenoma were recorded. Plasma calcitonin gene-related peptide and PACAP1-38 concentrations in pituitary adenoma patients within 72 h pre- and post-operation were measured. Primary outcome for HaPA patients were 50% reduction of moderate-to-severe headache days at 3 months after discharge. RESULTS: Sixty-three patients with pituitary adenoma were recruited, 33 (52.4%) of whom had headache. The patients who had HaPA presented with migraine-like (32.9%), tension-type-like (12.1%), and stabbing headache (9.1%). Non-functional adenoma was present in the majority of cases (82.5%). Surgical resection improved headache in 83.3% of cases at 3 month follow-up. Pre- and post-operative calcitonin gene-related peptide and PACAP1-38 levels were significantly higher in patients with headache than in those without headache (p < 0.05). Plasma calcitonin gene-related peptide and PACAP1-38 levels at 72 h post-operation were lower at 72 h after operation in patients who had greater improvement in headache compared with those who had little improvement, while plasma calcitonin gene-related peptide and PACAP1-38 levels were similar between these two groups preoperatively. CONCLUSIONS: Most pituitary adenoma patients have non-functional adenoma, and half of this group have HaPA, indicating that the ICHD-3 criteria for HaPA with the emphasis on secretion status need further modifications. Lower plasma calcitonin gene-related peptide and PACAP1-38 concentrations at 72 h after operation may predict a better outcome in patients with HaPA.

Diagnostic Value of D-dimer in Distinguishing between Spontaneous Subarachnoid Hemorrhage and Nontraumatic Acute Headache.

BACKGROUND: Spontaneous subarachnoid hemorrhage (SSAH) and nontraumatic acute headache patients presented with symptoms similar to headache. This study was to investigate the diagnostic value of D-dimer (DD) in distinguishing patients with SSAH from those with nontraumatic acute headache. METHODS: This retrospective study was performed and data were gathered from medical records of patients with acute headache symptoms from the Emergency Department and Neurology Clinics who were admitted to the Fourth Affiliated Hospital Zhejiang University School of Medicine between January 2015 and January 2019. Of the total 114 patients with headache symptoms enrolled in this study, 46 patients were diagnosed with SSAH (SAH group) and 68 cases with nontraumatic acute headache due to other causes (non-SAH group). The plasmatic levels of PT, INR, APTT, TT, FIB, and DD were compared between the two groups. Student's t-test of independent samples was adopted for comparing the mean between the two groups. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC). Comparison of AUC was performed using the Z-test. RESULTS: There were no significant statistical differences of the PT, INR, TT and FIB (all p > 0.05). The APTT was significantly decreased in the SSAH group compared with non-SAH group, while DD was significantly increased (all p < 0.001); moreover, AUC in distinguishing patients with SSAH from those with nontraumatic acute headache was 0.721 (95% confidence interval (CI), 0.629 to 0.801) for APTT and 0.886 (95% CI, 0.813 to 0.938) for DD. There was a significant statistical difference (p < 0.01). Finally, the cutoff values were 25.2s in distinguishing patients with SSAH from those with nontraumatic acute headache (specificity 73.53% and sensitivity 60.87%) for APTT and 0.31 mg/L (specificity 83.82% and sensitivity 84.78%) for DD. CONCLUSIONS: As an easy-to-obtain and potential biomarker, DD could demonstrate more accurate and reliable diagnostic value than APTT in distinguishing between SSAH and nontraumatic acute headache.

Comparison of the Diagnostic Values of Neutrophil, Neutrophil to Lymphocyte Ratio, and Platelet to Lymphocyte Ratio in Distinguishing Spontaneous Subarachnoid Hemorrhage from Nontraumatic Acute Headache.

BACKGROUND: To compare the diagnostic values of neutrophil, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) in distinguishing between spontaneous subarachnoid hemorrhage (SSAH) and non-traumatic acute headache. METHODS: Of the 125 patients with headache symptoms, 54 patients were diagnosed with SSAH (SAH group) and 71 cases with nontraumatic acute headache due to other causes (non-SAH group) were enrolled in this retrospective study. The levels of peripheral blood neutrophil counts, lymphocyte counts, platelet counts, NLR and PLR were recorded and compared between two groups. Student's t-test of independent samples was adopted for comparing the mean between two groups. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC). Comparison of AUC was performed using the Z-test. RESULTS: The levels of neutrophil counts, NLR and PLR were significantly increased in the SSAH group compared with the non-SAH group (all p < 0.01), while there were no significantly statistical differences of the lymphocyte counts and platelet counts (all p > 0.05); moreover, AUC in distinguishing between SSAH and nontraumatic acute headache was 0.918 (95% confidence interval (CI), 0.855 to 0.960) for neutrophil counts, 0.828 (95% CI, 0.751 to 0.890) for NLR and 0.616 (95% CI, 0.524 to 0.701) for PLR, and there were significant statistical differences (all p < 0.05) after pairwise comparison. Finally, the cutoff values were 4.7 x 109/L in distinguishing patients with SSAH from those with nontraumatic acute headache (specificity 88.73%, sensitivity 85.19% and Youden index 0.739) for neutrophil counts, 4 (specificity 98.59%, sensitivity 64.81% and Youden index 0.634) for NLR and 175 (specificity 92.96%, sensitivity 44.44% and Youden index 0.374) for PLR. CONCLUSIONS: Neutrophils can demonstrate more accurate and reliable diagnostic value than NLR and PLR, sug-gesting that it is a useful and potential tool in distinguishing between SSAH and nontraumatic acute headache.

Effects of Phyllanthus amarus PHYLLPROTM leaves on hangover symptoms: a randomized, double-blind, placebo-controlled crossover study.

CONTEXT: Phyllanthus amarus Schumach. and Thonn. (Euphorbiaceae) is traditionally known to improve general liver health. However, its effect on hangover is unknown. OBJECTIVE: This study evaluated PHYLLPRO™, a standardized ethanol extract of P. amarus leaves for protection against oxidative stress and recovery from hangover symptoms. MATERIAL AND METHODS: Ten days daily oral supplementation of 750 mg/day followed by intoxication was evaluated in a randomized placebo-controlled (containing only excipient), crossover study in 15 subjects (21-50 years old), for oxidative stress, liver damage, alleviating hangover symptoms (Hangover Severity Score: HSS) and mood improvement (Profile-of-Mood-Scores: POMS). RESULTS: PHYLLPRO™ was able to remove blood alcohol in the active group while the placebo group still had 0.05% at 12 h post-intoxication (p < 0.0001). For HSS, the active group showed reduced hangover symptoms while there were higher levels of nausea, headache, anorexia, tremulousness, diarrhoea and dizziness in the placebo group (p < 0.05) at hour 10 post-intoxication. Increased fatigue at hour 2 and tension (p > 0.05) from baseline to hour 22 was reported in the placebo group using POMS. Significant anti-inflammatory group effect favouring the active group, by the upregulation of cytokines IL-8 (p = 0.0014) and IL-10 (p = 0.0492) and immunomodulatory effects via IL-12p70 (p = 0.0304) were observed. The incidence of adverse events was similar between groups indicating the safety of PHYLLPRO™. DISCUSSION AND CONCLUSION: Preliminary findings of PHYLLPRO™ in managing hangover, inflammation and liver functions following intoxication, is demonstrated. Future studies on PHYLLPRO™ in protecting against oxidative stress and hangover in larger populations is warranted.

Coexistence of antiphospholipid antibodies and cephalalgia.

Background The occurrence of antiphospholipid antibodies (aPLs) and headache comorbidity in the presence or absence of underlying autoimmune diseases remains unclear. Aim The aim of this review was to summarize the relationship between headache and aPLs based on evidences from cohort studies and case reports, in addition to examining the treatment strategies that resolved headache in aPLs-positive individuals. Methods A comprehensive literature search was conducted through PubMed, ISI Web of Science and Google Scholar. A total of 559 articles were screened and the appropriate articles were selected based on quality and level of evidence. Results Cohort studies (n = 27) from Europe, North America and Asia demonstrated comorbidity of aPLs and headache in antiphospholipid syndrome, systemic lupus erythematosus (SLE) and neuropsychiatric SLE patients. Significantly higher association between migraine and aPLs was observed (n = 170/779; p < 0.0001) in individuals without any underlying diseases. Our analysis of shortlisted case reports (n = 17) showed that a higher frequency of anticardiolipin antibodies were present in subjects with different autoimmune disorders (70.6%). Corticosteroids were highly effective in resolving headache in aPLs-positive individuals. Conclusion Higher frequency of comorbidity between aPLs and headache was observed in healthy individuals and patient cases. Therefore, experimental studies are warranted to evaluate the aPLs-induced pathogenic mechanism of headache.

Headache and Ophthalmoparesis: Case Report of an "Atypical" Incomplete Miller-Fisher Syndrome.

OBJECTIVE: To expand the differential diagnosis of headache and ophthalmoparesis by describing a case report in which anti-GQ1b was demonstrated to be the cause. BACKGROUND: Anti-GQ1b antibody syndrome refers to a clinical spectrum of conditions that share common mechanisms and overlapping manifestations, including the Miller-Fisher syndrome, pharyngeal-cervical-brachial weakness, and Bickerstaff brainstem encephalitis. Rare atypical cases presenting as acute ophthalmoparesis (AO) without ataxia or areflexia have been described. Headache is a rare condition in these disorders. METHODS: A 49-year-old woman with no history of headaches began experiencing an acute severe bilateral throbbing headache associated with nausea and photophobia. Five days later, she developed constant binocular horizontal diplopia. RESULTS: Bilateral paresis of both sixth nerves was noted. Her ocular fundi, tendon reflexes, and other findings of the physical exam were normal. In addition, both a brain MRI performed with gadolinium and a lumbar puncture yielded normal results. Serum anti-GQ1b IgG was found to be positive. Her symptoms resolved completely following treatment with immunoglobulins (0.4 g/kg/day for 5 days). CONCLUSIONS: This is the first reported case of AO related to anti-GQ1b antibodies presenting with headache as its initial symptom. The presence of anti-GQ1b antibodies should be determined in patients with headache and AO of unknown origin. Immunoglobulins could hasten the resolution of symptoms in these patients.

A study of clinical, hematological, and biochemical profiles of patients with dengue viral infections in Northwest Ethiopia: implications for patient management.

BACKGROUND: Dengue is one of the most common arboviral diseases with increased outbreaks annually in tropical and subtropical areas. In Ethiopia, there are no data regarding clinical, hematological and biochemical parameters which are very important in the clinical management of dengue patients. Hence this study was carried out to provide the first baseline data of clinical, hematological and biochemical profiles of patients infected with dengue virus. METHODS: A cross-sectional study was carried out among febrile patients in northwest Ethiopia from March 2016 to May 2017. Blood samples were collected from dengue presumed cases and tested against dengue specific IgM antibody by enzyme-linked immunosorbent assay (ELISA). Those study participants who fulfilled the inclusion criteria were enrolled in the study. Clinical examination findings were recorded, hematological and biochemical parameters tests were done. RESULTS: During the study period, a total of 102 dengue cases were included in the study. Of these, there were 16 (15.7%) children and 86 (84.3%) adults between 1 and 76 year age. The most common clinical presentations followed by fever (100%) were a headache 89 (87.3%), myalgia 82 (80.4%), nausea/vomiting 71 (69.6%). The common hematological findings were thrombocytopenia 61 (59.8%), followed by anemia 45 (44.1%) and leucopenia 27 (26.5%) and the elevated levels of biochemical parameters were AST 46 (45.1%) and ALT in 18 (17.6%). CONCLUSIONS: This study highlights the most common clinical and laboratory profiles of dengue viral infections that could alert physicians to the likelihood of dengue virus infections in the study area.

Evaluation of Hematological Parameters in the Differentiation of Subarachnoid Hemorrhage and Other Headache Syndromes.

BACKGROUND: In this research, the aim was to compare hematological data for the differentiation of subarachnoid hemorrhage, migraine attack, and other headache syndromes during consultation in emergency service. METHODS: In this research, which was designed as retrospective case control study, hematological parameters (WBC, HgB, HCT, PLT, lymphocyte and neutrophile counts and neutrophile/lymphocyte rates) of the patients consulting to emergency service with SAH and migraine and other consulting patients complaining mainly from headache and having normal cranial CT were analysed. RESULTS: Sixty migraine attack patients (F/M:47/13), 57 SAH patients (F/M:30/27), and 53 patients except migraine having normal brain CT (F/M:36/17) who were consulted to emergency service with headache complaint were included in our research. WBC, Hct, HgB, MCV, PLT, MPV, LY, Neu counts, and NY/LY rates were found to differentiate between SAH and migraine. WBC, PLT, MPV, LY, and Neu rates were found to differentiate between SAH and HS patients. Only Hct, HgB, MCV, and NY/LY rates were found to differ meaningfully between SAH and migraine patients but these rates were not found to have meaningful difference between SAH and HS patients. In addition, an increase in WBC counts and NY/LY rates and decrease in MPV counts in ROC analysis were found to be more specific for SAH. CONCLUSIONS: WBC, HgB, HCT, PLT, lymphocyte and Neu counts, and NY/LY rates can indicate distinguishing SAH and migraine. WBC, HgB, HCT, PLT, lymphocyte and Neu counts can indicate to the clinician a differentiation of SAH and other headache syndromes.

Feasibility of serum CGRP measurement as a biomarker of chronic migraine: a critical reappraisal.

BACKGROUND: Calcitonin gene-related peptide (CGRP) has been reported as elevated in chronic migraine. We aimed to validate the role of interictal serum CGRP concentration in peripheral blood samples as a biomarker of chronic migraine. METHODS: We prospectively recruited patients with episodic and chronic migraine and normal controls (NCs) in the Samsung Medical Center between August 2015 and May 2016. Blood samples were collected interictally from antecubital veins per prespecified protocol. Serum CGRP measurement was performed in the central laboratory by a single experienced technician blinded to clinical information. Migraine subtype, headache days in the previous month, and the presence and characteristics of headache at ±2 days of measurement were evaluated at every visit. RESULTS: A total of 156 migraineurs (106 episodic and 50 chronic) and 27 NCs were recruited in this study. Compared to NCs (75.7 ± 20.07 pg/mL) and patients with episodic migraine (67.0 ± 20.70 pg/mL), patients with chronic migraine did not show an interictal elevation of serum CGRP levels (64.9 ± 15.32 pg/mL). Serum CGRP concentration was not associated with headache status (ictal vs. interictal), migraine subtype (migraine with vs. without aura), use of preventive or acute medications, and comorbid medication overuse. Higher serum CGRP concentration did not predict treatment response in patients with chronic migraine. CONCLUSIONS: Serum CGRP concentration may not be a feasible biomarker for chronic migraine. Further validation is necessary before CGRP can be used in the clinical practice.

Copeptin for risk stratification in non-traumatic headache in the emergency setting: a prospective multicenter observational cohort study.

BACKGROUND: In the emergency setting, non-traumatic headache is a benign symptom in 80% of cases, but serious underlying conditions need to be ruled out. Copeptin improves risk stratification in several acute diseases. Herein, we investigated the value of copeptin to discriminate between serious secondary headache and benign headache forms in the emergency setting. METHODS: Patients presenting with acute non-traumatic headache were prospectively enrolled into an observational cohort study. Copeptin was measured upon presentation to the emergency department. Primary endpoint was serious secondary headache defined by a neurologic cause requiring immediate treatment of the underlying disease. Secondary endpoint was the combination of mortality and hospitalization within 3 months. Two board-certified neurologist blinded to copeptin levels verified the endpoints after a structured 3-month-telephone interview. RESULTS: Of the 391 patients included, 75 (19%) had a serious secondary headache. Copeptin was associated with serious secondary headache (OR 2.03, 95%CI 1.52-2.70, p < 0.0001). Area under the curve (AUC) for copeptin to identify the primary endpoint was 0.70 (0.63-0.76). After adjusting for age > 50, focal-neurological abnormalities, and thunderclap onset of symptoms, copeptin remained an independent predictive factor for serious secondary headache (OR 1.74, 95%CI 1.26-2.39, p = 0.001). Moreover, copeptin improved the AUC of the multivariate logistic clinical model (p-LR-test < 0.001). Even though copeptin values were higher in patients reaching the secondary endpoint, this association was not significant in multivariate logistic regression. CONCLUSIONS: Copeptin was independently associated with serious secondary headache as compared to benign headaches forms. Copeptin may be a promising novel blood biomarker that should be further validated to rule out serious secondary headache in the emergency department. TRIAL REGISTRATION: Study Registration on 08/02/2010 as NCT01174901 at clinicaltrials.gov.

Headache prevalence following recovery from TTP and aHUS.

Thrombotic thrombocytopenia purpura (TTP) and atypical hemolytic uremic syndromes (aHUS) are distinct clinical disorders characterized by hemolytic anemia, thrombocytopenia, microthrombi, and end organ damage. TTP is characterized by a low ADAMTS13 activity level at diagnosis of <10 % ADAMTS13 activity, while aHUS is characterized as having >10 % ADAMTS13 activity. Despite clinical remission, survivors of thrombotic microangiopathy suffer significant comorbidity and decreased quality of life (QOL) than their healthy counterparts. The reason for this is unclear. Is it a lingering effect from their initial acute episode or ongoing subclinical injury/inflammation despite clinical remission? Common clinical complaints validated in practice include increased depression, deficits in memory, concentration, mood, and mental endurance. We suspect headaches may be an important clinical tool toward understanding patient morbidity and decreased QOL. To date, no studies report headache frequency or severity in this population. To answer this question, adult patients >3 months since their last acute episode of TTP or aHUS were approached to take a Headache Impact Test (HIT-6) survey. Between June 1, 2013 and May 30, 2014, 31 patients in remission (21 patients with prior TTP and 10 patients with prior aHUS) completed the HIT-6 survey. The survey scores were then compared to the HIT-6 normative population data established by Qualitymetric incorporated. Overall, TTP patients had a significantly higher average HIT-6 score of 59.9 compared to an average HIT-6 score of 51 seen in sex-matched controls (SD 9.6, p value 0.002). No significant difference was seen in the HIT-6 scores of aHUS patients. Of TTP patients studied, approximately 57 % (12/21) had three or more episodes and were >24 months since the last episode. The average time since last acute episode in TTP patients was 37.5 months. There was no significant correlation between TTP survivor HIT-6 scores and the number of prior episodes (1, 2, or >3) or timing from the last episode (3-6, 7-12, 13-24, or >24 months). About 19/21 (90 %) patients, who are TTP survivors, also had a normal ADAMTS13 activity level (>10 %) on the day of the survey. Our study suggests that headaches have significant impact on TTP survivors and should be followed in the clinical setting to prevent undue patient morbidity. Larger studies are needed to understand how headaches impact long-term survival and risk of relapse.

Dialysis headache in patients undergoing peritoneal dialysis and hemodialysis.

OBJECTIVES: Headache is among most frequently encountered neurological symptom during hemodialysis (HD), but still under investigated in peritoneal dialysis (PD) patients. The aim of this study was to assess the incidence and clinical characteristics of dialysis headache (DH) in HD and PD patients. MATERIAL AND METHODS: A total of 409 patients (91 on PD and 318 on HD) were interviewed using a structured questionnaire, designed according to the diagnostic criteria of the International Headache Classification of Headache Disorders from 2004. Patients with DH underwent a thorough neurological examination. RESULTS: DH was reported by 21 (6.6%) HD patients and 0 PD patients. PD patients had significantly lower serum sodium, potassium, calcium, phosphate, urea and creatinine, calcium-phosphate product, and diastolic blood pressure than HD patients. HD patients had significantly lower hemoglobin compared to PD patients. Primary renal disease was mostly parenchymal in HD patients, and vascular in PD patients. DH appeared more frequently in men, mostly during the third hour of HD. It lasted less than four hours, was bilateral, non-pulsating and without associated symptoms. CONCLUSION: Biochemical alterations may be implicated in the pathophysiology of DH. Specific features of DH might contribute to better understanding of this secondary headache disorder.